1824:. The neurons found in the ventral tegmental area, the ventromedial prefrontal cortex, and the nucleus accumbens shell are strongly implicated in addiction and the sensitization of neurons to stimulating drugs (such as amphetamines). Orexin producing neurons in these areas have been found to be primarily indicated in seeking behavior when externally stimulated by environmental signals such as stress. These neurons are in contrast to the lateral hypothalamic neurons, the perifornical-dorsal group of orexinergic neurons are involved in functions related to arousal and autonomic response. These neurons project inter-hypothalamically, as well as to the brainstem, where the release of orexin modulates various autonomic processes.
309:
286:
4601:
CB1-HcrtR1 heteromer compared with the HcrtR1-HcrtR1 homomer was reported (Ward et al., 2011b). These data provide unambiguous identification of CB1-HcrtR1 heteromerization, which has a substantial functional impact. ... The existence of a cross-talk between the hypocretinergic and endocannabinoid systems is strongly supported by their partially overlapping anatomical distribution and common role in several physiological and pathological processes. However, little is known about the mechanisms underlying this interaction.
1625:, with lethal consequences on a long-term basis. Sleep deprivation then leads to a lack of energy. In order to make up for this lack of energy, many people use high-carbohydrate and high-fat foods that ultimately can lead to poor health and weight gain. Other dietary nutrients, amino acids, also can activate orexin neurons, and they can suppress the glucose response of orexin neurons at physiological concentration, causing the energy balance that orexin maintains to be thrown off its normal cycle.
183:
208:
1549:, which is the loss of muscle tone in response to strong, usually positive, emotions. Dogs that lack a functional receptor for orexin have narcolepsy, while animals and people lacking the orexin neuropeptide itself also have narcolepsy. Organisms with narcolepsy were also found to experience REM sleep at any time of day, suggesting an alteration of function of REM sleep which can lead to hypnagogic hallucinations (hallucinations that occur as an organism goes to sleep).
1343:. To this end, they used transgenic cell lines that expressed individual orphan receptors and then exposed them to different potential ligands. They found that the orexin peptides activated the cells expressing the orexin receptors and went on to find orexin peptide expression specifically in the hypothalamus. Additionally, when either orexin peptide was administered to rats it stimulated feeding, giving rise to the name 'orexin'.
315:
214:
1561:, as would be expected if orexin were primarily an appetite stimulating peptide. Another indication that deficits of orexin cause narcolepsy is that depriving monkeys of sleep for 30–36 hours and then injecting them with the neurochemical alleviates the cognitive deficiencies normally seen with such amount of sleep loss.
4710:
heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations available for cannabinoid receptors.
1346:
The nomenclature of the orexin/hypocretin system now recognizes the history of its discovery. "Hypocretin" refers to the gene or genetic products and "orexin" refers to the protein, reflecting the differing approaches that resulted in its discovery. The use of both terms is also a practical necessity
1331:
family, so they named hypocretin to stand for a hypothalamic member of the incretin family. These cells were first thought to reside and work only within the lateral hypothalamus area, but immunocytochemistry techniques revealed the various projections this area truly had to other parts of the brain.
1620:
inhibits orexin production). Orexin, as of 2007, is claimed to be a very important link between metabolism and sleep regulation. Such a relationship has been long suspected, based on the observation that long-term sleep deprivation in rodents dramatically increases food intake and energy metabolism,
1468:
expenditure, and modulates visceral function. The orexin system has been hypothesized function by exciting other neurons that produce neurotransmitters (such as the locus coeruleus), as well as by inhibiting neurons in the ventrolateral preoptic nucleus, which is a region of the brain whose neuronal
1716:
It has been observed that orexin, while implicated in addiction and depression, is also involved in the display of anhedonia in ADHD. Proper functioning of orexin has been shown to have a large degree of control over behaviors that are motivated by a need to survive, such as searching for food when
1595:
Orexin increases the craving for food, and correlates with the function of the substances that promote its production. Orexin is also shown to increase meal size by suppressing inhibitory postingestive feedback. However, some studies suggest that the stimulatory effects of orexin on feeding may be
1708:
High levels of orexin-A have been associated with happiness in human subjects, while low levels have been associated with sadness. The finding suggests that boosting levels of orexin-A could elevate mood in humans, being thus a possible future treatment for disorders like depression. Orexins have
4670:
OX1–CB1 dimerization was suggested to strongly potentiate orexin receptor signaling, but a likely explanation for the signal potentiation is, instead, offered by the ability of OX1 receptor signaling to produce 2-arachidonoyl glycerol, a CB1 receptor ligand, and a subsequent co-signaling of the
1540:
regulation. Genetic knockout mice lacking the gene for orexin were also reported to exhibit narcolepsy. Transitioning frequently and rapidly between sleep and wakefulness, these mice display many of the symptoms of narcolepsy. Researchers are using this animal model of narcolepsy to study the
1326:
reported the discovery of several genes in the rat brain, including one they dubbed "clone 35." Their work showed that clone 35 expression was limited to the lateral hypothalamus. They extracted selective DNA found in the lateral hypothalamus. They cloned this DNA and studied it using electron
4600:
Direct CB1-HcrtR1 interaction was first proposed in 2003 (Hilairet et al., 2003). Indeed, a 100-fold increase in the potency of hypocretin-1 to activate the ERK signaling was observed when CB1 and HcrtR1 were co-expressed ... In this study, a higher potency of hypocretin-1 to regulate
1852:
ESSENCE (Early
Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) is an umbrella term covering a wide range of neurodevelopmental disorders and difficulties (ADHD, developmental coordination disorder, autism spectrum disorder) as well as ESSENCE-associated conditions
4709:
Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. ... In conclusion, orexin receptors have a significant propensity to make homo- and
1641:
given drugs which targeted the orexin system lost interest in alcohol despite being given free access in experiments. Wild type mice that were treated with morphine were found to be at a higher risk of developing addiction when compared to mice that did not produce orexin.
50:
1556:
also increases orexin-A transmission. The orexin system may thus be more important in the regulation of energy expenditure than in the regulation of food intake. In fact, orexin-deficient people with narcolepsy have increased obesity rather than decreased
1611:
is a short-term factor secreted by the stomach just before an expected meal, and strongly promotes food intake. Orexin-producing cells have been shown to be inhibited by leptin (through the leptin receptor pathway), but are activated by ghrelin and
1463:
The orexin system was initially suggested to be primarily involved in the stimulation of food intake, based on the finding that central administration of orexin-A and -B increased food intake. In addition, it stimulates wakefulness, regulates
3732:
Ida T, Nakahara K, Katayama T, Murakami N, Nakazato M (March 1999). "Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats".
1853:(behavioural phenotype syndromes, some neurological conditions and disorders, and severe early-onset mental disorders). Orexin/hypocretin system dysfunction might be associated with many symptoms in a variety of ESSENCE.
5874:
López JM, Sanz-Morello B, González A (November 2014). "Organization of the orexin/hypocretin system in the brain of two basal actinopterygian fishes, the cladistians
Polypterus senegalus and Erpetoichthys calabaricus".
1660:, a brain region that regulates cravings and contains orexin-1 receptors, lost the desire to smoke. However, other studies in rats using the dual orexin receptor antagonist TCS 1102 have not found similar effects.
5192:
Soffin EM, Gill CH, Brough SJ, Jerman JC, Davies CH (June 2004). "Pharmacological characterisation of the orexin receptor subtype mediating postsynaptic excitation in the rat dorsal raphe nucleus".
4683:
Jäntti MH, Mandrika I, Kukkonen JP (March 2014). "Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors".
2531:
Gotter AL, Webber AL, Coleman PJ, Renger JJ, Winrow CJ (July 2012). "International Union of Basic and
Clinical Pharmacology. LXXXVI. Orexin receptor function, nomenclature and pharmacology".
1303:
to reflect the orexigenic (appetite-stimulating) activity of these peptides. In their 1998 paper describing these neuropeptides, they also reported discovery of two orexin receptors, dubbed
1296:
1322:
The two groups also took different approaches towards their discovery. One team was interested in finding new genes that were expressed in the hypothalamus. In 1996, scientists from the
3819:
Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, et al. (February 2007). "Promotion of sleep by targeting the orexin system in rats, dogs and humans".
1505:
influences to determine whether an animal should be asleep, or awake and active. Orexin neurons strongly excite various brain nuclei with important roles in wakefulness including the
1352:
5008:
Yamanaka A, Muraki Y, Ichiki K, Tsujino N, Kilduff TS, Goto K, Sakurai T (July 2006). "Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner".
1914:
orexin is able to increase cognition in primates, especially under sleep deprived situations, which may provide an opportunity for the treatment of excessive daytime sleepiness.
6694:
1603:
that occurs in mice due to a habitual high-fat diet leads to a reduction in signalling by orexin receptor-2, and that orexin receptors may be a future therapeutic target.
322:
221:
2041:
1700:
pathway because this pathway inhibitor (LY294002) completely blocks OXA effects in adipocytes. The link between OXA and lipid metabolism is currently being studied.
1924:
Orexins are also thought to have potential implications in learning and aiding in fending off diseases such as dementia and other disorders that impair cognition.
1579:
alpha locus. In conjunction, these genetic anomalies cause the immune system to attack and kill the critical orexin neurons. Hence the absence of orexin-producing
6647:
1997:
1552:
Central administration of orexin-A strongly promotes wakefulness, increases body temperature and locomotion, and elicits a strong increase in energy expenditure.
5970:
2221:
Sutcliffe JG, de Lecea L (October 2000). "The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding".
6567:
4863:"Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and postsynaptic mechanisms: tonic depression of the hypothalamic arousal system"
1405:; orexin-B is a linear 28 amino acid residue peptide. Although these peptides are produced by a very small population of cells in the lateral and posterior
5346:
Grimaldi D, Silvani A, Benarroch EE, Cortelli P (January 2014). "Orexin/hypocretin system and autonomic control: new insights and clinical correlations".
1921:
in rats is feasible, indicating the development of alternative therapeutic strategies in addition to pharmacological interventions to treat narcolepsy.
864:
1717:
an organism is starving. When orexin does not function as intended, it impairs an organism's ability to feel pleasure from strongly motivated actions.
845:
144:
1885:
6687:
1568:(HLA) complex. Furthermore, genome-wide analysis shows that, in addition to the HLA variant, people with narcolepsy also exhibit a specific genetic
6193:
1208:. They project widely throughout the central nervous system, regulating wakefulness, feeding, and other behaviours. There are two types of orexin
5149:
Frederick-Duus D, Guyton MF, Fadel J (November 2007). "Food-elicited increases in cortical acetylcholine release require orexin transmission".
3527:"Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates"
3212:"Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat"
7046:
4298:"Orexin A stimulates glucose uptake, lipid accumulation and adiponectin secretion from 3T3-L1 adipocytes and isolated primary rat adipocytes"
2153:
1977:
4724:"Adenosine inhibits activity of hypocretin/orexin neurons by the A1 receptor in the lateral hypothalamus: a possible sleep-promoting effect"
2135:
1865:(Belsomra), which works by blocking both orexin receptors. Suvorexant has undergone three phase III trials and was approved in 2014 by the
1754:
1645:
Studies of orexin involvement in nicotine addiction have had mixed results. For example, blocking the orexin-1 receptor with the selective
2740:"Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations"
2500:
308:
6680:
1071:
1064:
2390:"Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior"
285:
7061:
5963:
5255:
2808:
2329:
2189:
5096:
Bernard R, Lydic R, Baghdoyan HA (October 2003). "Hypocretin-1 causes G protein activation and increases ACh release in rat pons".
5544:"Orexin/Hypocretin System Dysfunction in ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations)"
4087:
2967:"Activation of the rostral nucleus accumbens shell by optogenetics induces cataplexy-like behavior in orexin neuron-ablated mice"
2930:
Wong KK, Ng SY, Lee LT, Ng HK, Chow BK (April 2011). "Orexins and their receptors from fish to mammals: a comparative approach".
1731:
1375:
with approximately 50% sequence identity, produced by cleavage of a single precursor protein. This precursor protein is known as
5642:
4671:
receptors (Haj-Dahmane and Shen, 2005; Turunen et al., 2012; Jäntti et al., 2013). However, this does not preclude dimerization.
4511:"Group III metabotropic glutamate receptors maintain tonic inhibition of excitatory synaptic input to hypocretin/orexin neurons"
7051:
6557:
2122:
2101:
1866:
1808:
Orexinergic neurons can be differentiated into two groups based on connectivity and functionality. Orexinergic neurons in the
6867:
6714:
5939:
5816:
3065:"An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis"
2234:
1821:
1424:
1417:
207:
182:
2118:
2061:
47:
6145:
2834:"Characterisation of the binding of [3H]-SB-674042, a novel nonpeptide antagonist, to the human orexin-1 receptor"
1458:
3907:"The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions"
2689:"The physiological role of orexin/hypocretin neurons in the regulation of sleep/wakefulness and neuroendocrine functions"
2097:
6572:
5956:
3014:
Martins L, Seoane-Collazo P, Contreras C, González-García I, Martínez-Sánchez N, González F, et al. (August 2016).
1813:
1542:
124:
5238:
Mahler SV, Smith RJ, Moorman DE, Sartor GC, Aston-Jones G (2012). "Multiple roles for orexin/hypocretin in addiction".
6186:
6110:
6032:
2744:
2883:"Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR"
321:
220:
2508:
1774:
1410:
1323:
1319:
R or OX2). Masashi
Yanagisawa and Emmanuel Mignot were awarded the Breakthrough Prize in 2022 for this discovery.
5493:"Orexin/hypocretin system dysfunction in patients with Takotsubo syndrome: A novel pathophysiological explanation"
1327:
microscopy. Neurotransmitters found in this area were oddly similar to the gut hormone, secretin, a member of the
6592:
6087:
4296:
Skrzypski M, T Le T, Kaczmarek P, Pruszynska-Oszmalek E, Pietrzak P, Szczepankiewicz D, et al. (July 2011).
1896:
314:
213:
5053:
Ohno K, Sakurai T (January 2008). "Orexin neuronal circuitry: role in the regulation of sleep and wakefulness".
1709:
also been hypothesized to aid in the development of resilience to the stress response, as their activity in the
5924:
5815:
Arias-Carrión O, Murillo-Rodriguez E, Xu M, Blanco-Centurion C, Drucker-Colín R, Shiromani PJ (December 2004).
1841:
909:
132:
5668:
4390:"Is this peptide a key to happiness? Findings suggests possible new treatment for depression, other disorders"
2576:"Overview of the most prevalent hypothalamus-specific mRNAs, as identified by directional tag PCR subtraction"
2049:
1832:
Orexin/hypocretin system dysfunction might be associated with a variety of disorders and medical conditions.
1911:
1565:
1287:
In 1998, reports of the discovery of orexin/hypocretin were published nearly simultaneously. Luis de Lecea,
1219:
Orexin was discovered in 1998 almost simultaneously by two independent groups of researchers working on the
1213:
890:
5618:
5297:
Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P, Richardson KA (February 2010).
3500:
1279:. There is considerable similarity between the orexin system in the rat brain and that in the human brain.
7056:
6642:
6179:
6120:
5017:
1817:
1735:
1465:
1312:
1304:
1291:, and colleagues reported the discovery of the hypocretin system at the same time as Takeshi Sakurai from
3302:"The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene"
4339:"Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction"
3862:
Sakurai T (March 2007). "The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness".
1746:
196:
2045:
5930:
3776:
Tsuneki H, Wada T, Sasaoka T (March 2010). "Role of orexin in the regulation of glucose homeostasis".
6617:
6612:
6602:
6587:
6020:
4350:
4250:
4091:
3993:
3261:"Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep"
3166:
2587:
2450:
1990:
1809:
1486:
1478:
1205:
5391:"Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review"
3658:
111:
6444:
5022:
1918:
1653:
1501:. Studies indicate that a major role of the orexin system is to integrate metabolic, circadian and
6965:
6802:
6251:
4616:
4611:
4606:
4165:
Chieffi S, Carotenuto M, Monda V, Valenzano A, Villano I, Precenzano F, et al. (2017-05-31).
2574:
Gautvik KM, de Lecea L, Gautvik VT, Danielson PE, Tranque P, Dopazo A, et al. (August 1996).
1633:
Preliminary research shows potential for orexin blockers in the treatment of cocaine, opioid, and
6920:
6706:
6276:
6102:
6062:
5900:
5817:"Transplantation of hypocretin neurons into the pontine reticular formation: preliminary results"
5695:
5371:
5217:
5174:
5131:
5078:
4389:
4216:
4019:
3956:
3887:
3844:
3801:
3758:
3380:
3331:
2814:
2556:
2419:
2246:
1889:
1481:(BAT) activity via the sympathetic nervous system to enhance energy expenditure. Although orexin
1292:
1268:
156:
2388:
Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. (February 1998).
1197:), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.
1047:
1026:
1000:
979:
6925:
6886:
5389:
Al-Kuraishy HM, Abdulhadi MH, Hussien NR, Al-Niemi MS, Rasheed HA, Al-Gareeb AI (26 Jun 2020).
4239:"The dual orexin receptor antagonist TCS1102 does not affect reinstatement of nicotine-seeking"
3609:
Hallmayer J, Faraco J, Lin L, Hesselson S, Winkelmann J, Kawashima M, et al. (June 2009).
2881:
Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, et al. (September 1999).
7015:
6847:
6782:
6777:
6281:
6220:
6037:
5892:
5849:
5797:
5756:
5575:
5524:
5473:
5422:
5363:
5328:
5279:
5261:
5251:
5209:
5166:
5123:
5070:
5035:
4990:
4941:
4892:
4843:
4794:
4773:"Cholinergic regulation of orexin/hypocretin neurons through M(3) muscarinic receptor in mice"
4753:
4700:
4661:
4591:
4540:
4491:
4440:
4376:
4319:
4278:
4198:
4147:
4068:
4011:
3938:
3879:
3836:
3793:
3750:
3714:
3640:
3591:
3556:
3478:
3429:
3372:
3349:
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, et al. (August 1999).
3323:
3282:
3241:
3192:
3135:
3094:
3045:
2996:
2947:
2912:
2863:
2804:
2773:
2720:
2664:
2615:
2548:
2478:
2411:
2365:
2325:
2317:
2295:
2238:
2185:
2177:
2036:
1870:
1840:
Orexin/hypocretin system dysfunction has been proposed as a novel pathophysiological model of
1646:
1553:
1533:
1336:
and structures associated with it (including the amygdala, septum, and basal forebrain area).
104:
40:
7000:
6995:
6990:
6792:
6787:
4039:"Orexin/hypocretin signaling at the orexin 1 receptor regulates cue-elicited cocaine-seeking"
1607:
is a hormone produced by fat cells and acts as a long-term internal measure of energy state.
1193:, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or
6896:
6881:
6738:
6733:
5884:
5839:
5831:
5787:
5746:
5738:
5707:
5565:
5555:
5514:
5504:
5463:
5453:
5412:
5402:
5355:
5318:
5310:
5269:
5243:
5201:
5158:
5113:
5105:
5062:
5027:
4980:
4972:
4931:
4923:
4912:"Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor"
4910:
Tsujino N, Yamanaka A, Ichiki K, Muraki Y, Kilduff TS, Yagami K, et al. (August 2005).
4882:
4874:
4833:
4825:
4784:
4743:
4735:
4692:
4651:
4641:
4581:
4571:
4530:
4522:
4481:
4471:
4460:"Neurobiology of the Orexin System and Its Potential Role in the Regulation of Hedonic Tone"
4430:
4422:
4366:
4358:
4309:
4268:
4258:
4188:
4178:
4137:
4129:
4058:
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4001:
3928:
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3871:
3828:
3785:
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3704:
3696:
3630:
3622:
3583:
3546:
3538:
3468:
3460:
3419:
3411:
3362:
3313:
3272:
3231:
3223:
3182:
3174:
3125:
3084:
3076:
3035:
3027:
2986:
2978:
2939:
2902:
2894:
2853:
2845:
2796:
2763:
2753:
2710:
2700:
2654:
2646:
2605:
2595:
2540:
2468:
2458:
2437:
de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. (January 1998).
2401:
2357:
2285:
2277:
2230:
1710:
1129:
401:
332:
276:
231:
6728:
3464:
2281:
2028:
6852:
6703:
6607:
6332:
6322:
6025:
5440:
Villano I, La Marra M, Di Maio G, Monda V, Chieffi S, Guatteo E, et al. (July 2022).
3496:
3016:"A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance"
1762:
1681:
1576:
1558:
1413:
1387:
1340:
376:
152:
4607:
Figure 1: Schematic of brain CB1 expression and orexinergic neurons expressing OX1 or OX2
5299:"Lateral hypothalamic orexin/hypocretin neurons: A role in reward-seeking and addiction"
4354:
4254:
3997:
3170:
3114:"Orexin is required for brown adipose tissue development, differentiation, and function"
2591:
2454:
1713:
was found to decrease depressive symptoms by activating GABAergic neurons at that site.
1449:
The orexins are strongly conserved peptides, found in all major classes of vertebrates.
6627:
6622:
6355:
6350:
6327:
6229:
6155:
6072:
6010:
5844:
5792:
5775:
5751:
5726:
5570:
5543:
5519:
5492:
5468:
5441:
5417:
5390:
5323:
5298:
5274:
5247:
5162:
4985:
4960:
4936:
4911:
4887:
4862:
4838:
4813:
4748:
4723:
4656:
4629:
4586:
4559:
4535:
4510:
4486:
4459:
4435:
4410:
4371:
4338:
4273:
4238:
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4166:
4142:
4117:
4063:
4038:
3933:
3906:
3709:
3684:
3635:
3610:
3551:
3526:
3473:
3448:
3424:
3399:
3398:
Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE (July 2004).
3277:
3260:
3236:
3227:
3211:
3187:
3154:
3153:
Kakizaki M, Tsuneoka Y, Takase K, Kim SJ, Choi J, Ikkyu A, et al. (October 2019).
3089:
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3015:
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2800:
2768:
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2634:
2290:
2265:
1778:
1770:
1657:
1525:
1510:
1402:
1288:
1220:
4814:"Serotonergic regulation of the orexin/hypocretin neurons through the 5-HT1A receptor"
4560:"Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far"
4095:
3746:
3367:
3350:
3318:
3301:
2738:
Mogavero MP, Silvani A, Lanza G, DelRosso LM, Ferini-Strambi L, Ferri R (2023-01-22).
2406:
2389:
779:
774:
769:
764:
759:
754:
749:
744:
739:
734:
729:
724:
719:
714:
709:
704:
699:
694:
689:
684:
668:
663:
658:
653:
648:
643:
638:
633:
628:
623:
618:
602:
597:
592:
7040:
6930:
6304:
6299:
6266:
6015:
6000:
5205:
5109:
4054:
3789:
2818:
2610:
2575:
2473:
2438:
1982:
1802:
1794:
1742:
1600:
1518:
1482:
1398:
1333:
579:
5904:
5221:
5178:
5135:
3848:
3805:
3762:
3384:
2423:
2250:
1958:
136:
6980:
6955:
6901:
6891:
6797:
6632:
6508:
6503:
6498:
6493:
6460:
6455:
6206:
5983:
5920:
5888:
5375:
5314:
5082:
4976:
4927:
4878:
4829:
4526:
4023:
3957:"Neurotransmitter Orexin Associated With Pleasure And Reward Pathways In The Brain"
3891:
3683:
Baird JP, Choe A, Loveland JL, Beck J, Mahoney CE, Lord JS, Grigg LA (March 2009).
3542:
3415:
3080:
2560:
2024:
1900:
1878:
1613:
1584:
1521:
systems and appear to play an important role in stabilizing wakefulness and sleep.
1409:, they send projections throughout the brain. The orexin peptides bind to the two
1406:
1372:
1166:
394:
173:
5857:
5725:
Nixon JP, Mavanji V, Butterick TA, Billington CJ, Kotz CM, Teske JA (March 2015).
5690:
3335:
2002:
5359:
4263:
3685:"Orexin-A hyperphagia: hindbrain participation in consummatory feeding responses"
3031:
2832:
Langmead CJ, Jerman JC, Brough SJ, Scott C, Porter RA, Herdon HJ (January 2004).
1970:
160:
7025:
7005:
6985:
6960:
6857:
6817:
6637:
6547:
6475:
6450:
6386:
6371:
6291:
6261:
6246:
6115:
6092:
6067:
6042:
5066:
4337:
Blouin AM, Fried I, Wilson CL, Staba RJ, Behnke EJ, Lam HA, et al. (2013).
3587:
2943:
2348:
Boss C, Roch C (August 2015). "Recent trends in orexin research--2010 to 2015".
2158:
National Center for
Biotechnology Information, U.S. National Library of Medicine
2140:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1874:
1693:
1685:
1498:
1174:
4961:"Direct and indirect inhibition by catecholamines of hypocretin/orexin neurons"
4696:
3300:
Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, et al. (August 1999).
3178:
3130:
3113:
2982:
2650:
2580:
Proceedings of the
National Academy of Sciences of the United States of America
2443:
Proceedings of the
National Academy of Sciences of the United States of America
2439:"The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity"
2361:
2208:
477:
7020:
7010:
6975:
6970:
6950:
6945:
6940:
6842:
6822:
6812:
6807:
6772:
6767:
6762:
6652:
6439:
6403:
6393:
6376:
6342:
6314:
6271:
6125:
6077:
6057:
6052:
5979:
5835:
5742:
5509:
4812:
Muraki Y, Yamanaka A, Tsujino N, Kilduff TS, Goto K, Sakurai T (August 2004).
4426:
4314:
4297:
2074:
1862:
1677:
1649:
1634:
1622:
1529:
1502:
1384:
1190:
293:
190:
140:
6672:
5694:
for "Role of the Orexin
Receptor System in Stress, Sleep and Cocaine Use" at
5265:
4646:
4576:
4476:
4183:
3923:
2705:
1917:
A study has reported that transplantation of orexin neurons into the pontine
1730:
Orexinergic neurons have been shown to be sensitive to inputs from Group III
1668:
Orexin-A (OXA) has been demonstrated to have a direct effect on an aspect of
1339:
On the other hand, Sakurai and colleagues were studying the orexin system as
6837:
6832:
6827:
6577:
6562:
6408:
6398:
6381:
6238:
6150:
6135:
6005:
5948:
3351:"Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation"
2600:
1798:
1689:
1638:
1546:
1545:, inability to consolidate wakefulness in the day (and sleep at night), and
1514:
1194:
809:
537:
415:
360:
347:
259:
246:
148:
5896:
5853:
5801:
5760:
5579:
5528:
5477:
5458:
5426:
5367:
5332:
5283:
5213:
5170:
5127:
5074:
5039:
4994:
4945:
4896:
4847:
4798:
4789:
4772:
4757:
4704:
4665:
4595:
4544:
4495:
4444:
4380:
4323:
4282:
4202:
4151:
4133:
4072:
4015:
3942:
3883:
3840:
3797:
3754:
3718:
3644:
3595:
3560:
3482:
3433:
3376:
3327:
3286:
3196:
3139:
3098:
3049:
3000:
2951:
2916:
2898:
2867:
2849:
2777:
2724:
2668:
2552:
2369:
2299:
2242:
1596:
due to general arousal without necessarily increasing overall food intake.
1351:
and "OX" is used to refer to the pharmacology of the peptide system by the
6171:
5031:
4739:
3245:
2619:
2544:
2482:
2463:
2415:
1986:
1869:(FDA) after being denied approval the year before. The other FDA-approved
1111:
1106:
6914:
6910:
6751:
6747:
6552:
6531:
6526:
6470:
6130:
6047:
5118:
4612:
Figure 2: Synaptic signaling mechanisms in cannabinoid and orexin systems
4411:"Orexin prevents depressive-like behavior by promoting stress resilience"
3700:
3574:
Klein J, Sato A (September 2000). "The HLA system. Second of two parts".
2965:
Kawashima S, Lou F, Kusumoto-Yoshida I, Hao L, Kuwaki T (February 2023).
2178:"24. Orexigenic Hypothalamic Peptides Behavior and Feeding - 24.5 Orexin"
1965:
1569:
1506:
1368:
1364:
1328:
1247:
1186:
1182:
1178:
1095:
954:
935:
5560:
5407:
4006:
3981:
3611:"Narcolepsy is strongly associated with the T-cell receptor alpha locus"
2758:
2633:
Ebrahim IO, Howard RS, Kopelman MD, Sharief MK, Williams AJ (May 2002).
1401:(17q21). Orexin-A is 33 amino acid residues long and has two intrachain
750:
protein kinase C-activating G protein-coupled receptor signaling pathway
6597:
6582:
6202:
6140:
5992:
4362:
1790:
1782:
1673:
1617:
1608:
1348:
1276:
1252:
1209:
1204:
in the human brain, located predominantly in the perifornical area and
1201:
1170:
921:
876:
740:
phospholipase C-activating G protein-coupled receptor signaling pathway
1888:
registered a clinical trial for the use of suvorexant for people with
1861:
The orexin/hypocretin system is the target of the insomnia medication
81:
77:
73:
69:
3259:
Lu J, Bjorkum AA, Xu M, Gaus SE, Shiromani PJ, Saper CB (June 2002).
2056:
1786:
1604:
1580:
1573:
1232:
1079:
831:
3875:
2235:
10.1002/1097-4547(20001015)62:2<161::AID-JNR1>3.0.CO;2-1
1812:
group are closely associated with reward related functions, such as
3832:
3626:
1564:
In humans, narcolepsy is associated with a specific variant of the
1438:
with approximately equal affinity while orexin-B binds mainly to OX
6431:
6082:
3982:"A role for lateral hypothalamic orexin neurons in reward seeking"
1669:
1537:
1223:
5446:
International
Journal of Environmental Research and Public Health
4628:
Thompson MD, Xhaard H, Sakurai T, Rainero I, Kukkonen JP (2014).
3665:. American Association for the Advancement of Science. 2009-05-03
3155:"Differential Roles of Each Orexin Receptor Signaling in Obesity"
794:
790:
4116:
Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B (July 2006).
3659:"Narcolepsy is an autoimmune disorder, Stanford researcher says"
3525:
Deadwyler SA, Porrino L, Siegel JM, Hampson RE (December 2007).
2018:
1953:
1697:
1391:
1264:
128:
6676:
6175:
5952:
4217:"Blocking A Neuropeptide Receptor Decreases Nicotine Addiction"
16:
Neuropeptide that regulates arousal, wakefulness, and appetite.
6657:
5242:. Progress in Brain Research. Vol. 198. pp. 79–121.
3449:"Orexin receptors: pharmacology and therapeutic opportunities"
2266:"Orexin receptors: pharmacology and therapeutic opportunities"
1489:(BAT), subsequent report has shown normal development of BAT.
5776:"Narcolepsy: current treatment options and future approaches"
4617:
Figure 3: Schematic of brain pathways involved in food intake
1347:
because "HCRT" is the standard gene symbol in databases like
2322:
The Orexin/Hypocretin System: Physiology and Pathophysiology
2318:"3. Orexin Projections and Localization of Orexin Receptors"
5593:
5542:
Knez R, Stevanovic D, Fernell E, Gillberg C (15 Nov 2022).
3210:
Sherin JE, Elmquist JK, Torrealba F, Saper CB (June 1998).
1892:. They plan to measure cue reactivity, anxiety and stress.
1696:. These effects are thought to be mostly conferred via the
1141:
4409:
Ji MJ, Zhang XY, Chen Z, Wang JJ, Zhu JN (February 2019).
3063:
Tupone D, Madden CJ, Cano G, Morrison SF (November 2011).
1903:(Quviviq) for sleep initiation and maintenance disorders.
1524:
The discovery that an orexin receptor mutation causes the
1132:
725:
positive regulation of cytosolic calcium ion concentration
5940:
Orexin receptor antagonists: A new class of sleeping pill
5727:"Sleep disorders, obesity, and aging: the role of orexin"
4630:"OX1 and OX2 orexin/hypocretin receptor pharmacogenetics"
1297:
University of Texas Southwestern Medical Center at Dallas
1150:
4861:
Fu LY, Acuna-Goycolea C, van den Pol AN (October 2004).
384:
3400:"Behavioral state instability in orexin knock-out mice"
1536:
subsequently indicated a major role for this system in
1680:
and that increased energy uptake is stored as lipids (
1477:
Many studies support that the orexin neurons regulate
1353:
International Union of Basic and Clinical Pharmacology
1237:
meaning "appetite" in Greek; the other group named it
5442:"Physiological Role of Orexinergic System for Health"
4558:
Flores A, Maldonado R, Berrendero F (December 2013).
4509:
Acuna-Goycolea C, Li Y, Van Den Pol AN (March 2004).
4118:"The orexin system regulates alcohol-seeking in rats"
3980:
Harris GC, Wimmer M, Aston-Jones G (September 2005).
1793:. Orexinergic neurons themselves regulate release of
1656:
in rats and that smokers who sustained damage to the
1371:(hypocretin-1 and hypocretin-2). They are excitatory
1153:
1147:
1144:
549:
115:, OX, PPOX, hypocretin neuropeptide precursor, NRCLP1
2073:
The exon architecture of orexin is conserved in all
1138:
720:
positive regulation of transmission of nerve impulse
715:
negative regulation of transmission of nerve impulse
6866:
6713:
6540:
6517:
6486:
6430:
6421:
6364:
6341:
6313:
6290:
6237:
6228:
6213:
6101:
5991:
4685:
Biochemical and Biophysical Research Communications
2055:
2035:
2017:
2012:
1996:
1976:
1964:
1952:
1944:
1939:
1934:
1135:
1040:
1019:
993:
972:
2114:
2112:
2110:
2093:
2091:
2089:
1739:
1583:in people with narcolepsy may be the result of an
1469:activity is imperative to proper sleep function.
770:positive regulation of cold-induced thermogenesis
331:
230:
2501:"The brain chemicals that control what we enjoy"
5619:"FDA approves new type of sleep drug, Belsomra"
4037:Smith RJ, See RE, Aston-Jones G (August 2009).
3501:"Snorting a Brain Chemical Could Replace Sleep"
3112:Sellayah D, Bharaj P, Sikder D (October 2011).
2526:
2524:
6648:Pituitary adenylate cyclase-activating peptide
5233:
5231:
2383:
2381:
2379:
2119:GRCm38: Ensembl release 89: ENSMUSG00000045471
705:negative regulation of potassium ion transport
6688:
6568:Cocaine- and amphetamine-regulated transcript
6187:
5964:
2180:. In Preedy VR, Watson RR, Martin CR (eds.).
1816:. These neurons preferentially innervate the
8:
3453:Annual Review of Pharmacology and Toxicology
2350:Bioorganic & Medicinal Chemistry Letters
2270:Annual Review of Pharmacology and Toxicology
1332:A majority of these projections reached the
765:G protein-coupled receptor signaling pathway
735:positive regulation of calcium ion transport
5491:Knez R, Niksic M, Omerovic E (3 Nov 2022).
4167:"Orexin System: The Key for a Healthy Life"
2098:GRCh38: Ensembl release 89: ENSG00000161610
6695:
6681:
6673:
6427:
6234:
6194:
6180:
6172:
5971:
5957:
5949:
5643:"Dayvigo- lemborexant tablet, film coated"
2795:(2 ed.). Elsevier. pp. 133–135.
2494:
2492:
2203:
2201:
2009:
805:
575:
372:
271:
168:
58:
5923:at the U.S. National Library of Medicine
5843:
5791:
5750:
5569:
5559:
5518:
5508:
5467:
5457:
5416:
5406:
5322:
5273:
5117:
5021:
4984:
4935:
4886:
4837:
4788:
4771:Ohno K, Hondo M, Sakurai T (March 2008).
4747:
4655:
4645:
4585:
4575:
4534:
4485:
4475:
4434:
4370:
4313:
4272:
4262:
4192:
4182:
4141:
4062:
4005:
3932:
3922:
3708:
3634:
3550:
3472:
3423:
3366:
3317:
3276:
3235:
3186:
3129:
3088:
3039:
2990:
2906:
2857:
2767:
2757:
2714:
2704:
2658:
2609:
2599:
2472:
2462:
2405:
2289:
1886:University of Texas Health Science Center
1245:thalamus and bears a weak resemblance to
1200:There are 50,000–80,000 orexin-producing
760:regulation of signaling receptor activity
4237:Khoo SY, McNally GP, Clemens KJ (2017).
2639:Journal of the Royal Society of Medicine
2311:
2309:
2182:Handbook of Behavior, Food and Nutrition
1485:were reported to show maldevelopment of
730:regulation of neurotransmitter secretion
4458:Katzman MA, Katzman MP (January 2022).
2343:
2341:
2171:
2169:
2167:
2085:
5780:Neuropsychiatric Disease and Treatment
5548:Neuropsychiatric Disease and Treatment
3465:10.1146/annurev-pharmtox-010510-100528
2682:
2680:
2678:
2282:10.1146/annurev-pharmtox-010510-100528
1931:
700:negative regulation of DNA replication
18:
4959:Li Y, van den Pol AN (January 2005).
3905:Inutsuka A, Yamanaka A (2013-03-06).
3447:Scammell TE, Winrow CJ (2011-02-10).
2932:General and Comparative Endocrinology
2264:Scammell TE, Winrow CJ (2011-02-10).
2176:Davis JF, Choi DL, Benoit SC (2011).
1442:and is 5 times less potent at OX
336:
297:
292:
235:
194:
189:
7:
5497:Frontiers in Cardiovascular Medicine
5098:The European Journal of Neuroscience
4043:The European Journal of Neuroscience
5649:. U.S. National Library of Medicine
4777:Journal of Pharmacological Sciences
3576:The New England Journal of Medicine
5623:Food and Drug Administration (FDA)
5248:10.1016/B978-0-444-59489-1.00007-0
5163:10.1016/j.neuroscience.2007.07.061
4088:"Hope in fight against alcoholism"
3228:10.1523/JNEUROSCI.18-12-04705.1998
2801:10.1016/B978-0-12-820649-2.00036-X
2320:. In Nishino S, Sakurai T (eds.).
1430:, with orexin-A binding to both OX
1037:
1016:
990:
969:
945:
926:
900:
881:
855:
836:
598:type 1 hypocretin receptor binding
593:type 2 hypocretin receptor binding
554:
472:
410:
389:
14:
685:excitatory postsynaptic potential
5206:10.1016/j.neuropharm.2004.02.014
5110:10.1046/j.1460-9568.2003.02905.x
4055:10.1111/j.1460-9568.2009.06844.x
3790:10.1111/j.1748-1716.2009.02008.x
2223:Journal of Neuroscience Research
1732:metabotropic glutamate receptors
1692:and stimulates the secretion of
1275:is used to refer to the encoded
1241:, because it is produced in the
1128:
488:dorsomedial hypothalamic nucleus
320:
313:
307:
284:
219:
212:
206:
181:
6558:Calcitonin gene-related peptide
6021:Dronabinol/Tetrahydrocannabinol
5669:""Quviviq- daridorexant tablet"
5055:Frontiers in Neuroendocrinology
4722:Liu ZW, Gao XB (January 2007).
4396:(Press release). March 7, 2013.
4122:British Journal of Pharmacology
2887:British Journal of Pharmacology
2838:British Journal of Pharmacology
2687:Inutsuka A, Yamanaka A (2013).
2316:Marcus JN, Elmquist JK (2006).
2207:Stanford Center for Narcolepsy
1867:US Food and Drug Administration
1541:disease. Narcolepsy results in
1363:There are two types of orexin:
654:perinuclear region of cytoplasm
7026:Vornorexant (ORN-0829, TS-142)
6858:Vornorexant (ORN-0829, TS-142)
6853:Tebideutorexant (JNJ-61393215)
5889:10.1016/j.peptides.2014.08.011
5315:10.1016/j.brainres.2009.09.106
4977:10.1523/JNEUROSCI.4015-04.2005
4928:10.1523/JNEUROSCI.1193-05.2005
4879:10.1523/JNEUROSCI.2268-04.2004
4830:10.1523/JNEUROSCI.1027-04.2004
4527:10.1523/JNEUROSCI.5416-03.2004
4219:. ScienceDaily LLC. 2008-12-01
3543:10.1523/JNEUROSCI.3878-07.2007
3416:10.1523/JNEUROSCI.0586-04.2004
3081:10.1523/JNEUROSCI.3909-11.2011
2791:Nakamachi T (2021). "Orexin".
2635:"The hypocretin/orexin system"
1822:ventromedial prefrontal cortex
1299:reported the discovery of the
695:neuropeptide signaling pathway
690:chemical synaptic transmission
538:More reference expression data
1:
6146:Melanin-concentrating hormone
5617:Ventura J, ed. (2014-08-31).
5594:"BELSOMRA® (suvorexant) C-IV"
3747:10.1016/S0006-8993(99)01131-2
3368:10.1016/S0092-8674(00)81973-X
3319:10.1016/S0092-8674(00)81965-0
2407:10.1016/S0092-8674(00)80949-6
2013:Available protein structures:
1599:Review findings suggest that
1459:Orexinergic projection system
603:neuropeptide hormone activity
305:
204:
7047:Genes on human chromosome 17
6573:Delta-sleep-inducing peptide
5931:Compare Different Sleep Aids
5360:10.1212/WNL.0000000000000045
4264:10.1371/journal.pone.0173967
4086:Helen Puttick (2006-12-26).
3864:Nature Reviews. Neuroscience
3032:10.1016/j.celrep.2016.07.045
2184:. Springer. pp. 361–2.
1814:conditioned place preference
1543:excessive daytime sleepiness
1181:. It exists in the forms of
6033:Medroxyprogesterone acetate
5067:10.1016/j.yfrne.2007.08.001
4965:The Journal of Neuroscience
4916:The Journal of Neuroscience
4867:The Journal of Neuroscience
4818:The Journal of Neuroscience
4515:The Journal of Neuroscience
3588:10.1056/NEJM200009143431106
3531:The Journal of Neuroscience
3404:The Journal of Neuroscience
3265:The Journal of Neuroscience
3216:The Journal of Neuroscience
3069:The Journal of Neuroscience
2944:10.1016/j.ygcen.2011.01.001
2745:Nature and Science of Sleep
1775:cholecystokinin A receptors
1672:metabolism. OXA stimulates
644:rough endoplasmic reticulum
496:nucleus of stria terminalis
7078:
5010:Journal of Neurophysiology
4728:Journal of Neurophysiology
4697:10.1016/j.bbrc.2014.02.026
3911:Frontiers in Endocrinology
3179:10.1016/j.isci.2019.09.003
3131:10.1016/j.cmet.2011.08.010
2983:10.1038/s41598-023-29488-x
2693:Frontiers in Endocrinology
2651:10.1177/014107680209500503
2509:Royal Society of Chemistry
2362:10.1016/j.bmcl.2015.05.012
1844:(acute failure syndrome).
1456:
1324:Scripps Research Institute
1263:) is used to refer to the
1189:. The most common form of
1072:Chr 11: 100.65 – 100.65 Mb
6823:Nivasorexant (ACT-539313)
6593:Gastrin-releasing peptide
5944:National Sleep Foundation
5935:National Sleep Foundation
5743:10.1016/j.arr.2014.11.001
5712:European Medicines Agency
5510:10.3389/fcvm.2022.1016369
4634:Frontiers in Neuroscience
4564:Frontiers in Neuroscience
4427:10.1038/s41380-018-0127-0
4315:10.1007/s00125-011-2152-2
2324:. Springer. p. 195.
2154:"Mouse PubMed Reference:"
2136:"Human PubMed Reference:"
2008:
1897:European Medicines Agency
1828:Orexin system dysfunction
1110:
1105:
1101:
1094:
1078:
1059:
1044:
1023:
1012:
997:
976:
965:
952:
948:
933:
929:
920:
907:
903:
888:
884:
875:
862:
858:
843:
839:
830:
815:
808:
804:
788:
578:
574:
562:
557:
548:
535:
484:
475:
422:
413:
383:
375:
371:
354:
341:
304:
283:
274:
270:
253:
240:
203:
180:
171:
167:
122:
119:
109:
102:
97:
66:
61:
44:
39:
34:
30:
26:
21:
7062:Orexin receptor agonists
5925:Medical Subject Headings
5774:Billiard M (June 2008).
5240:Orexin/Hypocretin System
4647:10.3389/fnins.2014.00057
4577:10.3389/fnins.2013.00256
4477:10.3390/brainsci12020150
4184:10.3389/fphys.2017.00357
3924:10.3389/fendo.2013.00018
3507:. Wired News, Condé Nast
2706:10.3389/fendo.2013.00018
2499:Extance A (2022-11-07).
1637:addiction. For example,
1497:Orexin seems to promote
1212:and two types of orexin
1065:Chr 17: 42.18 – 42.19 Mb
6966:Fazamorexant (YZJ-1139)
6931:Suntinorexton (TAK-861)
6803:Fazamorexant (YZJ-1139)
6131:Cortisol/Hydrocortisone
5836:10.1093/sleep/27.8.1465
5731:Ageing Research Reviews
4171:Frontiers in Physiology
2601:10.1073/pnas.93.16.8733
2533:Pharmacological Reviews
2211:(retrieved 27-Mar-2012)
1566:human leukocyte antigen
755:temperature homeostasis
7052:Molecular neuroscience
6976:GSK-649868 (SB-649868)
6902:Firazorexton (TAK-994)
6892:Danavorexton (TAK-925)
6813:GSK-649868 (SB-649868)
6643:Pancreatic polypeptide
6121:Agouti-related peptide
5688:Clinical trial number
5459:10.3390/ijerph19148353
4790:10.1254/jphs.FP0071986
4134:10.1038/sj.bjp.0706789
2899:10.1038/sj.bjp.0702780
2850:10.1038/sj.bjp.0705610
1899:authorized the use of
1818:ventral tegmental area
1736:cannabinoid receptor 1
1684:). OXA thus increases
1313:Orexin receptor type 2
1305:Orexin receptor type 1
780:response to starvation
508:lumbar spinal ganglion
430:pancreatic ductal cell
5032:10.1152/jn.01361.2005
4740:10.1152/jn.00873.2006
4343:Nature Communications
2545:10.1124/pr.111.005546
2464:10.1073/pnas.95.1.322
1743:receptor heterodimers
1226:. One group named it
649:endoplasmic reticulum
299:Chromosome 11 (mouse)
197:Chromosome 17 (human)
6783:C4X-3256 (INDV-2000)
6588:Galanin-like peptide
4415:Molecular Psychiatry
3701:10.1210/en.2008-0293
2793:Handbook of Hormones
1907:Other potential uses
1810:lateral hypothalamic
1487:brown adipose tissue
1479:brown adipose tissue
1473:Brown fat activation
1206:lateral hypothalamus
619:extracellular region
338:11 D|11 63.6 cM
62:List of PDB id codes
35:Available structures
5980:Appetite stimulants
5714:. 22 February 2022.
5561:10.2147/NDT.S358373
5408:10.4103/bc.bc_42_19
4355:2013NatCo...4.1547B
4255:2017PLoSO..1273967K
4007:10.1038/nature04071
3998:2005Natur.437..556H
3537:(52): 14239–14247.
3171:2019iSci...20....1K
3075:(44): 15944–15955.
2759:10.2147/NSS.S201994
2592:1996PNAS...93.8733G
2455:1998PNAS...95..322D
1919:reticular formation
1688:. It also inhibits
1654:self-administration
669:cytoplasmic vesicle
6111:ACTH/Corticotropin
6063:Omega-3 fatty acid
5696:ClinicalTrials.gov
4615: •
4610: •
4605: •
4363:10.1038/ncomms2461
2971:Scientific Reports
2505:chemistryworld.com
1890:cocaine dependence
1871:orexin antagonists
1842:Takotsubo syndrome
1836:Takotsubo syndrome
1534:Doberman Pinschers
1293:Masashi Yanagisawa
910:ENSMUSG00000045471
678:Biological process
612:Cellular component
586:Molecular function
7034:
7033:
6670:
6669:
6666:
6665:
6417:
6416:
6169:
6168:
6161:Orexin/Hypocretin
6038:Megestrol acetate
5395:Brain Circulation
5194:Neuropharmacology
4922:(32): 7459–7469.
4873:(40): 8741–8751.
4824:(32): 7159–7166.
4521:(12): 3013–3022.
3992:(7058): 556–559.
3778:Acta Physiologica
3410:(28): 6291–6300.
3271:(11): 4568–4576.
3222:(12): 4705–4721.
2586:(16): 8733–8738.
2356:(15): 2875–2887.
2071:
2070:
2067:
2066:
2062:structure summary
1726:Neurotransmitters
1676:uptake in 3T3-L1
1652:reduced nicotine
1647:orexin antagonist
1554:Sleep deprivation
1411:G-protein coupled
1161:), also known as
1121:
1120:
1117:
1116:
1090:
1089:
1055:
1054:
1034:
1033:
1008:
1007:
987:
986:
961:
960:
942:
941:
916:
915:
897:
896:
871:
870:
852:
851:
800:
799:
664:secretory granule
570:
569:
566:
565:
544:
543:
531:
530:
469:
468:
442:nucleus accumbens
367:
366:
266:
265:
93:
92:
89:
88:
45:Ortholog search:
7069:
6697:
6690:
6683:
6674:
6428:
6235:
6196:
6189:
6182:
6173:
5973:
5966:
5959:
5950:
5909:
5908:
5871:
5865:
5864:
5862:
5856:. Archived from
5847:
5830:(8): 1465–1470.
5821:
5812:
5806:
5805:
5795:
5771:
5765:
5764:
5754:
5722:
5716:
5715:
5704:
5698:
5686:
5680:
5679:
5673:
5665:
5659:
5658:
5656:
5654:
5639:
5633:
5632:
5630:
5629:
5614:
5608:
5607:
5605:
5604:
5590:
5584:
5583:
5573:
5563:
5539:
5533:
5532:
5522:
5512:
5488:
5482:
5481:
5471:
5461:
5437:
5431:
5430:
5420:
5410:
5386:
5380:
5379:
5343:
5337:
5336:
5326:
5294:
5288:
5287:
5277:
5235:
5226:
5225:
5200:(8): 1168–1176.
5189:
5183:
5182:
5146:
5140:
5139:
5121:
5104:(7): 1775–1785.
5093:
5087:
5086:
5050:
5044:
5043:
5025:
5005:
4999:
4998:
4988:
4956:
4950:
4949:
4939:
4907:
4901:
4900:
4890:
4858:
4852:
4851:
4841:
4809:
4803:
4802:
4792:
4768:
4762:
4761:
4751:
4719:
4713:
4712:
4680:
4674:
4673:
4659:
4649:
4625:
4619:
4603:
4589:
4579:
4555:
4549:
4548:
4538:
4506:
4500:
4499:
4489:
4479:
4455:
4449:
4448:
4438:
4406:
4400:
4397:
4387:Lay summary in:
4384:
4374:
4334:
4328:
4327:
4317:
4308:(7): 1841–1852.
4293:
4287:
4286:
4276:
4266:
4234:
4228:
4227:
4225:
4224:
4213:
4207:
4206:
4196:
4186:
4162:
4156:
4155:
4145:
4113:
4107:
4106:
4104:
4103:
4094:. Archived from
4083:
4077:
4076:
4066:
4034:
4028:
4027:
4009:
3977:
3971:
3970:
3968:
3967:
3953:
3947:
3946:
3936:
3926:
3902:
3896:
3895:
3859:
3853:
3852:
3816:
3810:
3809:
3773:
3767:
3766:
3729:
3723:
3722:
3712:
3695:(3): 1202–1216.
3680:
3674:
3673:
3671:
3670:
3655:
3649:
3648:
3638:
3606:
3600:
3599:
3571:
3565:
3564:
3554:
3522:
3516:
3515:
3513:
3512:
3493:
3487:
3486:
3476:
3444:
3438:
3437:
3427:
3395:
3389:
3388:
3370:
3346:
3340:
3339:
3321:
3297:
3291:
3290:
3280:
3256:
3250:
3249:
3239:
3207:
3201:
3200:
3190:
3150:
3144:
3143:
3133:
3109:
3103:
3102:
3092:
3060:
3054:
3053:
3043:
3026:(8): 2231–2242.
3011:
3005:
3004:
2994:
2962:
2956:
2955:
2927:
2921:
2920:
2910:
2878:
2872:
2871:
2861:
2829:
2823:
2822:
2788:
2782:
2781:
2771:
2761:
2735:
2729:
2728:
2718:
2708:
2684:
2673:
2672:
2662:
2630:
2624:
2623:
2613:
2603:
2571:
2565:
2564:
2528:
2519:
2518:
2516:
2515:
2496:
2487:
2486:
2476:
2466:
2434:
2428:
2427:
2409:
2385:
2374:
2373:
2345:
2336:
2335:
2313:
2304:
2303:
2293:
2261:
2255:
2254:
2218:
2212:
2205:
2196:
2195:
2173:
2162:
2161:
2150:
2144:
2143:
2132:
2126:
2116:
2105:
2095:
2010:
1932:
1781:, as well as to
1741:
1711:ventral pallidum
1664:Lipid metabolism
1414:orexin receptors
1381:preprohypocretin
1341:orphan receptors
1160:
1159:
1156:
1155:
1152:
1149:
1146:
1143:
1140:
1137:
1134:
1103:
1102:
1074:
1067:
1050:
1038:
1029:
1017:
1013:RefSeq (protein)
1003:
991:
982:
970:
946:
927:
901:
882:
856:
837:
806:
710:feeding behavior
659:synaptic vesicle
576:
555:
540:
480:
478:Top expressed in
473:
458:substantia nigra
418:
416:Top expressed in
411:
390:
373:
363:
350:
339:
324:
317:
311:
300:
288:
272:
262:
249:
238:
223:
216:
210:
199:
185:
169:
163:
161:HCRT - orthologs
114:
107:
84:
59:
53:
32:
31:
19:
7077:
7076:
7072:
7071:
7070:
7068:
7067:
7066:
7037:
7036:
7035:
7030:
6871:
6862:
6718:
6709:
6704:Orexin receptor
6701:
6671:
6662:
6618:Neuropeptide VF
6613:Neuropeptide SF
6608:Neuropeptide FF
6603:Neuropeptide AF
6536:
6513:
6482:
6423:
6413:
6360:
6337:
6309:
6286:
6255:
6230:Opioid peptides
6224:
6209:
6200:
6170:
6165:
6097:
5987:
5977:
5917:
5912:
5873:
5872:
5868:
5860:
5819:
5814:
5813:
5809:
5773:
5772:
5768:
5724:
5723:
5719:
5706:
5705:
5701:
5687:
5683:
5671:
5667:
5666:
5662:
5652:
5650:
5641:
5640:
5636:
5627:
5625:
5616:
5615:
5611:
5602:
5600:
5592:
5591:
5587:
5541:
5540:
5536:
5490:
5489:
5485:
5439:
5438:
5434:
5388:
5387:
5383:
5345:
5344:
5340:
5296:
5295:
5291:
5258:
5237:
5236:
5229:
5191:
5190:
5186:
5148:
5147:
5143:
5095:
5094:
5090:
5052:
5051:
5047:
5007:
5006:
5002:
4958:
4957:
4953:
4909:
4908:
4904:
4860:
4859:
4855:
4811:
4810:
4806:
4770:
4769:
4765:
4721:
4720:
4716:
4682:
4681:
4677:
4627:
4626:
4622:
4614:
4609:
4604:
4557:
4556:
4552:
4508:
4507:
4503:
4457:
4456:
4452:
4408:
4407:
4403:
4388:
4336:
4335:
4331:
4295:
4294:
4290:
4249:(3): e0173967.
4236:
4235:
4231:
4222:
4220:
4215:
4214:
4210:
4164:
4163:
4159:
4115:
4114:
4110:
4101:
4099:
4085:
4084:
4080:
4036:
4035:
4031:
3979:
3978:
3974:
3965:
3963:
3955:
3954:
3950:
3904:
3903:
3899:
3876:10.1038/nrn2092
3861:
3860:
3856:
3821:Nature Medicine
3818:
3817:
3813:
3775:
3774:
3770:
3731:
3730:
3726:
3682:
3681:
3677:
3668:
3666:
3657:
3656:
3652:
3615:Nature Genetics
3608:
3607:
3603:
3582:(11): 782–786.
3573:
3572:
3568:
3524:
3523:
3519:
3510:
3508:
3497:Alexis Madrigal
3495:
3494:
3490:
3446:
3445:
3441:
3397:
3396:
3392:
3348:
3347:
3343:
3299:
3298:
3294:
3258:
3257:
3253:
3209:
3208:
3204:
3152:
3151:
3147:
3118:Cell Metabolism
3111:
3110:
3106:
3062:
3061:
3057:
3013:
3012:
3008:
2964:
2963:
2959:
2929:
2928:
2924:
2880:
2879:
2875:
2831:
2830:
2826:
2811:
2790:
2789:
2785:
2737:
2736:
2732:
2686:
2685:
2676:
2632:
2631:
2627:
2573:
2572:
2568:
2530:
2529:
2522:
2513:
2511:
2498:
2497:
2490:
2436:
2435:
2431:
2387:
2386:
2377:
2347:
2346:
2339:
2332:
2315:
2314:
2307:
2263:
2262:
2258:
2220:
2219:
2215:
2206:
2199:
2192:
2175:
2174:
2165:
2152:
2151:
2147:
2134:
2133:
2129:
2117:
2108:
2096:
2087:
2083:
1930:
1909:
1859:
1850:
1838:
1830:
1766:
1758:
1750:
1728:
1723:
1706:
1682:triacylglycerol
1666:
1631:
1593:
1495:
1475:
1461:
1455:
1445:
1441:
1437:
1433:
1428:
1421:
1403:disulfide bonds
1397:and located on
1390:encoded by the
1388:pre-pro-peptide
1383:) and is a 130
1361:
1318:
1310:
1285:
1169:that regulates
1131:
1127:
1112:View/Edit Mouse
1107:View/Edit Human
1070:
1063:
1060:Location (UCSC)
1046:
1025:
999:
978:
891:ENSG00000161610
784:
745:eating behavior
673:
607:
536:
527:
522:
518:
514:
510:
506:
502:
498:
494:
490:
476:
465:
460:
456:
452:
450:caudate nucleus
448:
444:
440:
436:
432:
428:
414:
358:
345:
337:
327:
326:
325:
318:
298:
275:Gene location (
257:
244:
236:
226:
225:
224:
217:
195:
172:Gene location (
123:
110:
103:
68:
46:
17:
12:
11:
5:
7075:
7073:
7065:
7064:
7059:
7054:
7049:
7039:
7038:
7032:
7031:
7029:
7028:
7023:
7018:
7013:
7008:
7003:
6998:
6993:
6988:
6983:
6978:
6973:
6968:
6963:
6958:
6953:
6948:
6943:
6934:
6933:
6928:
6923:
6918:
6904:
6899:
6894:
6889:
6884:
6875:
6873:
6869:
6864:
6863:
6861:
6860:
6855:
6850:
6845:
6840:
6835:
6830:
6825:
6820:
6815:
6810:
6805:
6800:
6795:
6790:
6785:
6780:
6775:
6770:
6765:
6756:
6755:
6741:
6736:
6731:
6722:
6720:
6716:
6711:
6710:
6702:
6700:
6699:
6692:
6685:
6677:
6668:
6667:
6664:
6663:
6661:
6660:
6655:
6650:
6645:
6640:
6635:
6630:
6628:Neuropeptide Y
6625:
6623:Neuropeptide S
6620:
6615:
6610:
6605:
6600:
6595:
6590:
6585:
6580:
6575:
6570:
6565:
6560:
6555:
6550:
6544:
6542:
6538:
6537:
6535:
6534:
6529:
6523:
6521:
6515:
6514:
6512:
6511:
6506:
6501:
6496:
6490:
6488:
6484:
6483:
6481:
6480:
6479:
6478:
6473:
6465:
6464:
6463:
6458:
6453:
6442:
6436:
6434:
6425:
6419:
6418:
6415:
6414:
6412:
6411:
6406:
6401:
6396:
6391:
6390:
6389:
6379:
6374:
6368:
6366:
6362:
6361:
6359:
6358:
6356:Leu-enkephalin
6353:
6351:Met-enkephalin
6347:
6345:
6339:
6338:
6336:
6335:
6330:
6325:
6319:
6317:
6311:
6310:
6308:
6307:
6302:
6296:
6294:
6288:
6287:
6285:
6284:
6282:β-Neoendorphin
6279:
6277:α-Neoendorphin
6274:
6269:
6264:
6259:
6258:
6257:
6253:
6243:
6241:
6232:
6226:
6225:
6217:
6215:
6211:
6210:
6201:
6199:
6198:
6191:
6184:
6176:
6167:
6166:
6164:
6163:
6158:
6156:Neuropeptide Y
6153:
6148:
6143:
6138:
6133:
6128:
6123:
6118:
6113:
6107:
6105:
6099:
6098:
6096:
6095:
6090:
6085:
6080:
6075:
6073:Pentoxifylline
6070:
6065:
6060:
6055:
6050:
6045:
6040:
6035:
6030:
6018:
6013:
6011:Cyproheptadine
6008:
6003:
5997:
5995:
5989:
5988:
5978:
5976:
5975:
5968:
5961:
5953:
5947:
5946:
5937:
5928:
5916:
5915:External links
5913:
5911:
5910:
5866:
5863:on 2016-03-03.
5807:
5786:(3): 557–566.
5766:
5717:
5699:
5681:
5660:
5634:
5609:
5585:
5534:
5483:
5432:
5381:
5354:(3): 271–278.
5338:
5303:Brain Research
5289:
5256:
5227:
5184:
5157:(3): 499–507.
5141:
5088:
5045:
5023:10.1.1.320.260
5016:(1): 284–298.
5000:
4971:(1): 173–183.
4951:
4902:
4853:
4804:
4783:(3): 485–491.
4763:
4734:(1): 837–848.
4714:
4691:(2): 486–490.
4675:
4620:
4550:
4501:
4464:Brain Sciences
4450:
4421:(2): 282–293.
4401:
4399:
4398:
4329:
4288:
4229:
4208:
4157:
4128:(6): 752–759.
4108:
4078:
4049:(3): 493–503.
4029:
3972:
3948:
3897:
3870:(3): 171–181.
3854:
3833:10.1038/nm1544
3827:(2): 150–155.
3811:
3784:(3): 335–348.
3768:
3741:(2): 526–529.
3735:Brain Research
3724:
3675:
3650:
3627:10.1038/ng.372
3621:(6): 708–711.
3601:
3566:
3517:
3499:(2007-12-28).
3488:
3439:
3390:
3361:(4): 437–451.
3341:
3312:(3): 365–376.
3292:
3251:
3202:
3145:
3124:(4): 478–490.
3104:
3055:
3006:
2957:
2938:(2): 124–130.
2922:
2873:
2844:(2): 340–346.
2824:
2809:
2783:
2730:
2674:
2645:(5): 227–230.
2625:
2566:
2539:(3): 389–420.
2520:
2488:
2449:(1): 322–327.
2429:
2400:(4): 573–585.
2375:
2337:
2330:
2305:
2256:
2229:(2): 161–168.
2213:
2197:
2190:
2163:
2145:
2127:
2106:
2084:
2082:
2079:
2069:
2068:
2065:
2064:
2059:
2053:
2052:
2039:
2033:
2032:
2022:
2015:
2014:
2006:
2005:
2000:
1994:
1993:
1980:
1974:
1973:
1968:
1962:
1961:
1956:
1950:
1949:
1946:
1942:
1941:
1937:
1936:
1929:
1926:
1908:
1905:
1877:(Dayvigo) and
1858:
1855:
1849:
1846:
1837:
1834:
1829:
1826:
1779:catecholamines
1771:neuropeptide Y
1764:
1756:
1748:
1727:
1724:
1722:
1721:Orexin neurons
1719:
1705:
1702:
1665:
1662:
1630:
1627:
1592:
1589:
1526:sleep disorder
1511:norepinephrine
1494:
1491:
1474:
1471:
1454:
1451:
1443:
1439:
1435:
1431:
1426:
1419:
1360:
1357:
1316:
1311:R or OX1) and
1308:
1295:'s lab at the
1289:Thomas Kilduff
1284:
1281:
1255:. Officially,
1119:
1118:
1115:
1114:
1109:
1099:
1098:
1092:
1091:
1088:
1087:
1085:
1083:
1076:
1075:
1068:
1061:
1057:
1056:
1053:
1052:
1042:
1041:
1035:
1032:
1031:
1021:
1020:
1014:
1010:
1009:
1006:
1005:
995:
994:
988:
985:
984:
974:
973:
967:
963:
962:
959:
958:
950:
949:
943:
940:
939:
931:
930:
924:
918:
917:
914:
913:
905:
904:
898:
895:
894:
886:
885:
879:
873:
872:
869:
868:
860:
859:
853:
850:
849:
841:
840:
834:
828:
827:
822:
817:
813:
812:
802:
801:
798:
797:
786:
785:
783:
782:
777:
772:
767:
762:
757:
752:
747:
742:
737:
732:
727:
722:
717:
712:
707:
702:
697:
692:
687:
681:
679:
675:
674:
672:
671:
666:
661:
656:
651:
646:
641:
636:
631:
626:
621:
615:
613:
609:
608:
606:
605:
600:
595:
589:
587:
583:
582:
572:
571:
568:
567:
564:
563:
560:
559:
552:
546:
545:
542:
541:
533:
532:
529:
528:
526:
525:
521:
520:axial skeleton
517:
513:
509:
505:
501:
497:
493:
489:
485:
482:
481:
470:
467:
466:
464:
463:
459:
455:
451:
447:
443:
439:
435:
431:
427:
423:
420:
419:
407:
406:
398:
387:
381:
380:
377:RNA expression
369:
368:
365:
364:
356:
352:
351:
343:
340:
335:
329:
328:
319:
312:
306:
302:
301:
296:
290:
289:
281:
280:
268:
267:
264:
263:
255:
251:
250:
242:
239:
234:
228:
227:
218:
211:
205:
201:
200:
193:
187:
186:
178:
177:
165:
164:
121:
117:
116:
108:
100:
99:
95:
94:
91:
90:
87:
86:
64:
63:
55:
54:
43:
37:
36:
28:
27:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
7074:
7063:
7060:
7058:
7057:Neuropeptides
7055:
7053:
7050:
7048:
7045:
7044:
7042:
7027:
7024:
7022:
7019:
7017:
7014:
7012:
7009:
7007:
7004:
7002:
6999:
6997:
6994:
6992:
6989:
6987:
6984:
6982:
6979:
6977:
6974:
6972:
6969:
6967:
6964:
6962:
6959:
6957:
6954:
6952:
6949:
6947:
6944:
6942:
6939:
6936:
6935:
6932:
6929:
6927:
6924:
6922:
6919:
6916:
6912:
6908:
6905:
6903:
6900:
6898:
6895:
6893:
6890:
6888:
6885:
6883:
6880:
6877:
6876:
6874:
6872:
6865:
6859:
6856:
6854:
6851:
6849:
6846:
6844:
6841:
6839:
6836:
6834:
6831:
6829:
6826:
6824:
6821:
6819:
6816:
6814:
6811:
6809:
6806:
6804:
6801:
6799:
6796:
6794:
6791:
6789:
6786:
6784:
6781:
6779:
6776:
6774:
6771:
6769:
6766:
6764:
6761:
6758:
6757:
6753:
6749:
6745:
6742:
6740:
6737:
6735:
6732:
6730:
6727:
6724:
6723:
6721:
6719:
6712:
6708:
6705:
6698:
6693:
6691:
6686:
6684:
6679:
6678:
6675:
6659:
6656:
6654:
6651:
6649:
6646:
6644:
6641:
6639:
6636:
6634:
6631:
6629:
6626:
6624:
6621:
6619:
6616:
6614:
6611:
6609:
6606:
6604:
6601:
6599:
6596:
6594:
6591:
6589:
6586:
6584:
6581:
6579:
6576:
6574:
6571:
6569:
6566:
6564:
6561:
6559:
6556:
6554:
6551:
6549:
6546:
6545:
6543:
6539:
6533:
6530:
6528:
6525:
6524:
6522:
6520:
6516:
6510:
6507:
6505:
6502:
6500:
6497:
6495:
6492:
6491:
6489:
6485:
6477:
6474:
6472:
6469:
6468:
6466:
6462:
6459:
6457:
6454:
6452:
6449:
6448:
6446:
6443:
6441:
6438:
6437:
6435:
6433:
6429:
6426:
6424:neuropeptides
6420:
6410:
6407:
6405:
6402:
6400:
6397:
6395:
6392:
6388:
6385:
6384:
6383:
6380:
6378:
6375:
6373:
6370:
6369:
6367:
6363:
6357:
6354:
6352:
6349:
6348:
6346:
6344:
6340:
6334:
6331:
6329:
6326:
6324:
6321:
6320:
6318:
6316:
6312:
6306:
6305:Endomorphin-2
6303:
6301:
6300:Endomorphin-1
6298:
6297:
6295:
6293:
6289:
6283:
6280:
6278:
6275:
6273:
6270:
6268:
6267:Big dynorphin
6265:
6263:
6260:
6256:
6250:
6249:
6248:
6245:
6244:
6242:
6240:
6236:
6233:
6231:
6227:
6223:
6222:
6216:
6212:
6208:
6207:neuropeptides
6204:
6197:
6192:
6190:
6185:
6183:
6178:
6177:
6174:
6162:
6159:
6157:
6154:
6152:
6149:
6147:
6144:
6142:
6139:
6137:
6134:
6132:
6129:
6127:
6124:
6122:
6119:
6117:
6114:
6112:
6109:
6108:
6106:
6104:
6100:
6094:
6091:
6089:
6086:
6084:
6081:
6079:
6076:
6074:
6071:
6069:
6066:
6064:
6061:
6059:
6056:
6054:
6051:
6049:
6046:
6044:
6041:
6039:
6036:
6034:
6031:
6028:
6027:
6022:
6019:
6017:
6016:Dexamethasone
6014:
6012:
6009:
6007:
6004:
6002:
6001:Amitriptyline
5999:
5998:
5996:
5994:
5990:
5985:
5981:
5974:
5969:
5967:
5962:
5960:
5955:
5954:
5951:
5945:
5941:
5938:
5936:
5932:
5929:
5926:
5922:
5919:
5918:
5914:
5906:
5902:
5898:
5894:
5890:
5886:
5882:
5878:
5870:
5867:
5859:
5855:
5851:
5846:
5841:
5837:
5833:
5829:
5825:
5818:
5811:
5808:
5803:
5799:
5794:
5789:
5785:
5781:
5777:
5770:
5767:
5762:
5758:
5753:
5748:
5744:
5740:
5736:
5732:
5728:
5721:
5718:
5713:
5709:
5703:
5700:
5697:
5693:
5692:
5685:
5682:
5677:
5670:
5664:
5661:
5648:
5644:
5638:
5635:
5624:
5620:
5613:
5610:
5599:
5595:
5589:
5586:
5581:
5577:
5572:
5567:
5562:
5557:
5554:: 2683–2702.
5553:
5549:
5545:
5538:
5535:
5530:
5526:
5521:
5516:
5511:
5506:
5502:
5498:
5494:
5487:
5484:
5479:
5475:
5470:
5465:
5460:
5455:
5451:
5447:
5443:
5436:
5433:
5428:
5424:
5419:
5414:
5409:
5404:
5400:
5396:
5392:
5385:
5382:
5377:
5373:
5369:
5365:
5361:
5357:
5353:
5349:
5342:
5339:
5334:
5330:
5325:
5320:
5316:
5312:
5308:
5304:
5300:
5293:
5290:
5285:
5281:
5276:
5271:
5267:
5263:
5259:
5257:9780444594891
5253:
5249:
5245:
5241:
5234:
5232:
5228:
5223:
5219:
5215:
5211:
5207:
5203:
5199:
5195:
5188:
5185:
5180:
5176:
5172:
5168:
5164:
5160:
5156:
5152:
5145:
5142:
5137:
5133:
5129:
5125:
5120:
5119:2027.42/75751
5115:
5111:
5107:
5103:
5099:
5092:
5089:
5084:
5080:
5076:
5072:
5068:
5064:
5060:
5056:
5049:
5046:
5041:
5037:
5033:
5029:
5024:
5019:
5015:
5011:
5004:
5001:
4996:
4992:
4987:
4982:
4978:
4974:
4970:
4966:
4962:
4955:
4952:
4947:
4943:
4938:
4933:
4929:
4925:
4921:
4917:
4913:
4906:
4903:
4898:
4894:
4889:
4884:
4880:
4876:
4872:
4868:
4864:
4857:
4854:
4849:
4845:
4840:
4835:
4831:
4827:
4823:
4819:
4815:
4808:
4805:
4800:
4796:
4791:
4786:
4782:
4778:
4774:
4767:
4764:
4759:
4755:
4750:
4745:
4741:
4737:
4733:
4729:
4725:
4718:
4715:
4711:
4706:
4702:
4698:
4694:
4690:
4686:
4679:
4676:
4672:
4667:
4663:
4658:
4653:
4648:
4643:
4639:
4635:
4631:
4624:
4621:
4618:
4613:
4608:
4602:
4597:
4593:
4588:
4583:
4578:
4573:
4569:
4565:
4561:
4554:
4551:
4546:
4542:
4537:
4532:
4528:
4524:
4520:
4516:
4512:
4505:
4502:
4497:
4493:
4488:
4483:
4478:
4473:
4469:
4465:
4461:
4454:
4451:
4446:
4442:
4437:
4432:
4428:
4424:
4420:
4416:
4412:
4405:
4402:
4395:
4394:Science Daily
4391:
4386:
4385:
4382:
4378:
4373:
4368:
4364:
4360:
4356:
4352:
4348:
4344:
4340:
4333:
4330:
4325:
4321:
4316:
4311:
4307:
4303:
4299:
4292:
4289:
4284:
4280:
4275:
4270:
4265:
4260:
4256:
4252:
4248:
4244:
4240:
4233:
4230:
4218:
4212:
4209:
4204:
4200:
4195:
4190:
4185:
4180:
4176:
4172:
4168:
4161:
4158:
4153:
4149:
4144:
4139:
4135:
4131:
4127:
4123:
4119:
4112:
4109:
4098:on 2012-02-10
4097:
4093:
4089:
4082:
4079:
4074:
4070:
4065:
4060:
4056:
4052:
4048:
4044:
4040:
4033:
4030:
4025:
4021:
4017:
4013:
4008:
4003:
3999:
3995:
3991:
3987:
3983:
3976:
3973:
3962:
3958:
3952:
3949:
3944:
3940:
3935:
3930:
3925:
3920:
3916:
3912:
3908:
3901:
3898:
3893:
3889:
3885:
3881:
3877:
3873:
3869:
3865:
3858:
3855:
3850:
3846:
3842:
3838:
3834:
3830:
3826:
3822:
3815:
3812:
3807:
3803:
3799:
3795:
3791:
3787:
3783:
3779:
3772:
3769:
3764:
3760:
3756:
3752:
3748:
3744:
3740:
3736:
3728:
3725:
3720:
3716:
3711:
3706:
3702:
3698:
3694:
3690:
3689:Endocrinology
3686:
3679:
3676:
3664:
3660:
3654:
3651:
3646:
3642:
3637:
3632:
3628:
3624:
3620:
3616:
3612:
3605:
3602:
3597:
3593:
3589:
3585:
3581:
3577:
3570:
3567:
3562:
3558:
3553:
3548:
3544:
3540:
3536:
3532:
3528:
3521:
3518:
3506:
3502:
3498:
3492:
3489:
3484:
3480:
3475:
3470:
3466:
3462:
3458:
3454:
3450:
3443:
3440:
3435:
3431:
3426:
3421:
3417:
3413:
3409:
3405:
3401:
3394:
3391:
3386:
3382:
3378:
3374:
3369:
3364:
3360:
3356:
3352:
3345:
3342:
3337:
3333:
3329:
3325:
3320:
3315:
3311:
3307:
3303:
3296:
3293:
3288:
3284:
3279:
3274:
3270:
3266:
3262:
3255:
3252:
3247:
3243:
3238:
3233:
3229:
3225:
3221:
3217:
3213:
3206:
3203:
3198:
3194:
3189:
3184:
3180:
3176:
3172:
3168:
3164:
3160:
3156:
3149:
3146:
3141:
3137:
3132:
3127:
3123:
3119:
3115:
3108:
3105:
3100:
3096:
3091:
3086:
3082:
3078:
3074:
3070:
3066:
3059:
3056:
3051:
3047:
3042:
3037:
3033:
3029:
3025:
3021:
3017:
3010:
3007:
3002:
2998:
2993:
2988:
2984:
2980:
2976:
2972:
2968:
2961:
2958:
2953:
2949:
2945:
2941:
2937:
2933:
2926:
2923:
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2914:
2909:
2904:
2900:
2896:
2892:
2888:
2884:
2877:
2874:
2869:
2865:
2860:
2855:
2851:
2847:
2843:
2839:
2835:
2828:
2825:
2820:
2816:
2812:
2810:9780128206492
2806:
2802:
2798:
2794:
2787:
2784:
2779:
2775:
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2765:
2760:
2755:
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2747:
2746:
2741:
2734:
2731:
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2712:
2707:
2702:
2698:
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2648:
2644:
2640:
2636:
2629:
2626:
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2612:
2607:
2602:
2597:
2593:
2589:
2585:
2581:
2577:
2570:
2567:
2562:
2558:
2554:
2550:
2546:
2542:
2538:
2534:
2527:
2525:
2521:
2510:
2506:
2502:
2495:
2493:
2489:
2484:
2480:
2475:
2470:
2465:
2460:
2456:
2452:
2448:
2444:
2440:
2433:
2430:
2425:
2421:
2417:
2413:
2408:
2403:
2399:
2395:
2391:
2384:
2382:
2380:
2376:
2371:
2367:
2363:
2359:
2355:
2351:
2344:
2342:
2338:
2333:
2331:9781592599509
2327:
2323:
2319:
2312:
2310:
2306:
2301:
2297:
2292:
2287:
2283:
2279:
2275:
2271:
2267:
2260:
2257:
2252:
2248:
2244:
2240:
2236:
2232:
2228:
2224:
2217:
2214:
2210:
2204:
2202:
2198:
2193:
2191:9780387922713
2187:
2183:
2179:
2172:
2170:
2168:
2164:
2159:
2155:
2149:
2146:
2141:
2137:
2131:
2128:
2124:
2120:
2115:
2113:
2111:
2107:
2103:
2099:
2094:
2092:
2090:
2086:
2080:
2078:
2076:
2063:
2060:
2058:
2054:
2051:
2047:
2043:
2040:
2038:
2034:
2030:
2026:
2023:
2020:
2016:
2011:
2007:
2004:
2001:
1999:
1995:
1992:
1988:
1984:
1981:
1979:
1975:
1972:
1969:
1967:
1963:
1960:
1957:
1955:
1951:
1947:
1943:
1938:
1935:Prepro-orexin
1933:
1927:
1925:
1922:
1920:
1915:
1913:
1906:
1904:
1902:
1898:
1895:In 2022, the
1893:
1891:
1887:
1884:In 2016, the
1882:
1880:
1876:
1872:
1868:
1864:
1857:Clinical uses
1856:
1854:
1847:
1845:
1843:
1835:
1833:
1827:
1825:
1823:
1819:
1815:
1811:
1806:
1804:
1803:noradrenaline
1800:
1796:
1795:acetylcholine
1792:
1788:
1784:
1780:
1776:
1772:
1768:
1760:
1752:
1744:
1737:
1733:
1725:
1720:
1718:
1714:
1712:
1703:
1701:
1699:
1695:
1691:
1687:
1683:
1679:
1675:
1671:
1663:
1661:
1659:
1655:
1651:
1648:
1643:
1640:
1636:
1628:
1626:
1624:
1619:
1615:
1610:
1606:
1602:
1601:hyperglycemia
1597:
1590:
1588:
1586:
1582:
1578:
1575:
1571:
1567:
1562:
1560:
1555:
1550:
1548:
1544:
1539:
1535:
1531:
1527:
1522:
1520:
1519:acetylcholine
1516:
1512:
1508:
1504:
1500:
1492:
1490:
1488:
1484:
1483:knockout mice
1480:
1472:
1470:
1467:
1460:
1452:
1450:
1447:
1429:
1422:
1415:
1412:
1408:
1404:
1400:
1399:chromosome 17
1396:
1393:
1389:
1386:
1382:
1378:
1377:prepro-orexin
1374:
1373:neuropeptides
1370:
1366:
1358:
1356:
1354:
1350:
1344:
1342:
1337:
1335:
1334:limbic system
1330:
1325:
1320:
1314:
1306:
1302:
1298:
1294:
1290:
1282:
1280:
1278:
1274:
1270:
1266:
1262:
1258:
1254:
1250:
1249:
1244:
1240:
1236:
1234:
1229:
1225:
1222:
1217:
1215:
1211:
1207:
1203:
1198:
1196:
1192:
1188:
1184:
1180:
1176:
1172:
1168:
1164:
1158:
1125:
1113:
1108:
1104:
1100:
1097:
1093:
1086:
1084:
1081:
1077:
1073:
1069:
1066:
1062:
1058:
1051:
1049:
1043:
1039:
1036:
1030:
1028:
1022:
1018:
1015:
1011:
1004:
1002:
996:
992:
989:
983:
981:
975:
971:
968:
966:RefSeq (mRNA)
964:
957:
956:
951:
947:
944:
938:
937:
932:
928:
925:
923:
919:
912:
911:
906:
902:
899:
893:
892:
887:
883:
880:
878:
874:
867:
866:
861:
857:
854:
848:
847:
842:
838:
835:
833:
829:
826:
823:
821:
818:
814:
811:
807:
803:
796:
792:
787:
781:
778:
776:
773:
771:
768:
766:
763:
761:
758:
756:
753:
751:
748:
746:
743:
741:
738:
736:
733:
731:
728:
726:
723:
721:
718:
716:
713:
711:
708:
706:
703:
701:
698:
696:
693:
691:
688:
686:
683:
682:
680:
677:
676:
670:
667:
665:
662:
660:
657:
655:
652:
650:
647:
645:
642:
640:
639:cell junction
637:
635:
632:
630:
627:
625:
622:
620:
617:
616:
614:
611:
610:
604:
601:
599:
596:
594:
591:
590:
588:
585:
584:
581:
580:Gene ontology
577:
573:
561:
556:
553:
551:
547:
539:
534:
523:
519:
515:
511:
507:
503:
499:
495:
491:
487:
486:
483:
479:
474:
471:
461:
457:
454:muscle tissue
453:
449:
445:
441:
437:
433:
429:
425:
424:
421:
417:
412:
409:
408:
405:
403:
399:
397:
396:
392:
391:
388:
386:
382:
378:
374:
370:
362:
357:
353:
349:
344:
334:
330:
323:
316:
310:
303:
295:
291:
287:
282:
278:
273:
269:
261:
256:
252:
248:
243:
233:
229:
222:
215:
209:
202:
198:
192:
188:
184:
179:
175:
170:
166:
162:
158:
154:
150:
146:
142:
138:
134:
130:
126:
118:
113:
106:
101:
96:
85:
83:
79:
75:
71:
65:
60:
57:
56:
52:
49:
42:
38:
33:
29:
25:
20:
6981:JNJ-10397049
6956:Daridorexant
6938:Antagonists:
6937:
6906:
6878:
6798:Daridorexant
6760:Antagonists:
6759:
6743:
6725:
6633:Neurophysins
6518:
6461:Neurokinin B
6456:Neurokinin A
6292:Endomorphins
6218:
6160:
6088:Testosterone
6024:
5943:
5934:
5880:
5876:
5869:
5858:the original
5827:
5823:
5810:
5783:
5779:
5769:
5734:
5730:
5720:
5711:
5702:
5689:
5684:
5675:
5663:
5653:30 September
5651:. Retrieved
5646:
5637:
5626:. Retrieved
5622:
5612:
5601:. Retrieved
5597:
5588:
5551:
5547:
5537:
5500:
5496:
5486:
5452:(14): 8353.
5449:
5445:
5435:
5401:(2): 70–80.
5398:
5394:
5384:
5351:
5347:
5341:
5306:
5302:
5292:
5239:
5197:
5193:
5187:
5154:
5151:Neuroscience
5150:
5144:
5101:
5097:
5091:
5061:(1): 70–87.
5058:
5054:
5048:
5013:
5009:
5003:
4968:
4964:
4954:
4919:
4915:
4905:
4870:
4866:
4856:
4821:
4817:
4807:
4780:
4776:
4766:
4731:
4727:
4717:
4708:
4688:
4684:
4678:
4669:
4637:
4633:
4623:
4599:
4567:
4563:
4553:
4518:
4514:
4504:
4467:
4463:
4453:
4418:
4414:
4404:
4393:
4346:
4342:
4332:
4305:
4302:Diabetologia
4301:
4291:
4246:
4242:
4232:
4221:. Retrieved
4211:
4174:
4170:
4160:
4125:
4121:
4111:
4100:. Retrieved
4096:the original
4081:
4046:
4042:
4032:
3989:
3985:
3975:
3964:. Retrieved
3961:ScienceDaily
3960:
3951:
3914:
3910:
3900:
3867:
3863:
3857:
3824:
3820:
3814:
3781:
3777:
3771:
3738:
3734:
3727:
3692:
3688:
3678:
3667:. Retrieved
3662:
3653:
3618:
3614:
3604:
3579:
3575:
3569:
3534:
3530:
3520:
3509:. Retrieved
3504:
3491:
3456:
3452:
3442:
3407:
3403:
3393:
3358:
3354:
3344:
3309:
3305:
3295:
3268:
3264:
3254:
3219:
3215:
3205:
3162:
3158:
3148:
3121:
3117:
3107:
3072:
3068:
3058:
3023:
3020:Cell Reports
3019:
3009:
2974:
2970:
2960:
2935:
2931:
2925:
2890:
2886:
2876:
2841:
2837:
2827:
2792:
2786:
2749:
2743:
2733:
2696:
2692:
2642:
2638:
2628:
2583:
2579:
2569:
2536:
2532:
2512:. Retrieved
2504:
2446:
2442:
2432:
2397:
2393:
2353:
2349:
2321:
2273:
2269:
2259:
2226:
2222:
2216:
2181:
2157:
2148:
2139:
2130:
2072:
1923:
1916:
1910:
1901:daridorexant
1894:
1883:
1879:daridorexant
1860:
1851:
1839:
1831:
1807:
1761:, serotonin
1755:muscarinic M
1729:
1715:
1707:
1667:
1644:
1632:
1614:hypoglycemia
1598:
1594:
1563:
1551:
1523:
1496:
1476:
1462:
1448:
1407:hypothalamus
1394:
1380:
1376:
1362:
1345:
1338:
1321:
1300:
1286:
1272:
1260:
1256:
1246:
1242:
1238:
1231:
1227:
1218:
1199:
1167:neuropeptide
1162:
1123:
1122:
1045:
1024:
998:
977:
953:
934:
908:
889:
863:
844:
824:
819:
516:spermatocyte
426:hypothalamus
400:
393:
359:100,653,757
346:100,651,895
120:External IDs
67:
7006:Seltorexant
6986:Lemborexant
6921:Oveporexton
6818:Lemborexant
6638:Neurotensin
6548:Angiotensin
6487:Neuromedins
6476:Physalaemin
6451:Substance P
6445:Tachykinins
6440:Bradykinins
6387:Hemorphin-4
6372:Adrenorphin
6343:Enkephalins
6333:γ-Endorphin
6328:β-Endorphin
6323:α-Endorphin
6262:Dynorphin B
6252:Dynorphin A
6247:Dynorphin A
6116:Adiponectin
6093:Thalidomide
6068:Oxandrolone
6043:Mirtazapine
5691:NCT02785406
5503:: 1016369.
3459:: 243–266.
2977:(1): 2546.
2276:: 243–266.
2075:vertebrates
1998:OPM protein
1940:Identifiers
1881:(Quviviq).
1875:lemborexant
1773:receptors,
1747:adenosine A
1694:adiponectin
1686:lipogenesis
1591:Food intake
1499:wakefulness
1493:Wakefulness
1269:transcripts
1175:wakefulness
624:postsynapse
438:granulocyte
258:42,185,452
245:42,184,060
98:Identifiers
7041:Categories
7021:TCS-OX2-29
7011:Suvorexant
6971:Filorexant
6951:Almorexant
6946:ACT-462206
6941:ACT-335827
6843:Suvorexant
6808:Filorexant
6773:Almorexant
6768:ACT-462206
6763:ACT-335827
6707:modulators
6467:amphibian
6404:Spinorphin
6394:Nociceptin
6377:Amidorphin
6315:Endorphins
6272:Leumorphin
6239:Dynorphins
6126:Anandamide
6103:Endogenous
6078:Prednisone
6058:Olanzapine
6053:Nandrolone
5628:2015-10-31
5603:2015-10-31
4470:(2): 150.
4223:2009-02-11
4102:2007-02-11
4092:The Herald
3966:2018-05-08
3917:(18): 18.
3669:2009-05-31
3663:EurekAlert
3511:2008-02-05
2893:(1): 1–3.
2748:(Review).
2514:2023-04-04
2125:, May 2017
2104:, May 2017
2081:References
2025:structures
1912:Intranasal
1863:suvorexant
1678:adipocytes
1650:SB-334,867
1623:catabolism
1587:disorder.
1585:autoimmune
1530:narcolepsy
1503:sleep debt
1457:See also:
1385:amino acid
1257:hypocretin
1251:, another
1239:hypocretin
1191:narcolepsy
1163:hypocretin
500:blastocyst
462:cerebellum
404:(ortholog)
141:HomoloGene
6926:SB-668875
6887:ALKS-2680
6879:Agonists:
6838:SB-408124
6833:SB-334867
6828:RTIOX-276
6726:Agonists:
6578:FMRFamide
6563:Carnosine
6447:: mammal
6409:Valorphin
6399:Opiorphin
6382:Hemorphin
6151:Melatonin
6136:Cortisone
6006:Clonidine
5993:Exogenous
5883:: 23–37.
5737:: 63–73.
5708:"Quviviq"
5348:Neurology
5309:: 74–90.
5266:0079-6123
5018:CiteSeerX
2819:243394088
2752:: 17–38.
1971:IPR001704
1928:Evolution
1799:serotonin
1767:receptors
1759:receptors
1751:receptors
1690:lipolysis
1629:Addiction
1547:cataplexy
1515:histamine
1283:Discovery
1195:cataplexy
1048:NP_034540
1027:NP_001515
1001:NM_010410
980:NM_001524
810:Orthologs
629:cytoplasm
149:GeneCards
7016:TCS-1102
6848:TCS-1102
6778:AZD-4041
6553:Bombesin
6471:Kassinin
6221:hormones
6214:Hormones
6203:Peptides
6048:Nabilone
6026:Cannabis
5905:34333729
5897:25169954
5877:Peptides
5854:15683135
5802:18830438
5761:25462194
5647:DailyMed
5598:Belsomra
5580:36411777
5529:36407467
5478:35886210
5427:33033776
5368:24363130
5333:19815001
5284:22813971
5222:45872346
5214:15111023
5179:19452926
5171:17928158
5136:18515164
5128:14622212
5075:17910982
5040:16611835
4995:15634779
4946:16093397
4897:15470140
4848:15306649
4799:18344611
4758:17093123
4705:24530395
4666:24834023
4596:24391536
4545:15044540
4496:35203914
4445:30087452
4381:23462990
4349:: 1547.
4324:21505958
4283:28296947
4243:PLOS ONE
4203:28620314
4152:16751790
4073:19656173
4016:16100511
3943:23508038
3884:17299454
3849:40999737
3841:17259994
3806:23346403
3798:19489767
3763:39775146
3755:10064841
3719:19008313
3645:19412176
3596:10984567
3561:18160631
3483:21034217
3434:15254084
3385:89799178
3377:10481909
3328:10458611
3287:12040064
3197:31546102
3165:: 1–13.
3159:iScience
3140:21982708
3099:22049437
3050:27524625
3001:36781929
2952:21216246
2917:10498827
2868:14691055
2778:36713640
2725:23508038
2669:11983761
2553:22759794
2424:16294729
2370:26045032
2300:21034217
2251:33215844
2243:11020209
2121:–
2100:–
2042:RCSB PDB
1966:InterPro
1820:and the
1639:lab rats
1577:receptor
1570:mutation
1507:dopamine
1453:Function
1369:orexin-B
1365:orexin-A
1359:Isoforms
1329:incretin
1277:peptides
1271:, while
1248:secretin
1214:receptor
1187:orexin-B
1183:orexin-A
1179:appetite
1096:Wikidata
789:Sources:
524:meninges
7001:MK-8133
6996:MK-3697
6991:MK-1064
6793:CVN-766
6788:CR-5542
6653:RVD-Hpα
6598:Ghrelin
6583:Galanin
6519:Orexins
6141:Ghrelin
5921:orexins
5845:1201562
5793:2526380
5752:4467809
5676:fda.gov
5571:9675327
5520:9670121
5469:9323672
5418:7511915
5376:9209963
5324:2819557
5275:3643893
5083:7888110
4986:6725201
4937:6725310
4888:6729969
4839:6729168
4749:1783688
4657:4018553
4587:3868890
4570:: 256.
4536:6729849
4487:8870430
4436:6755988
4372:3595130
4351:Bibcode
4274:5351999
4251:Bibcode
4194:5450021
4177:: 357.
4143:1617074
4064:2771107
4024:4386257
3994:Bibcode
3934:3589707
3892:8932862
3710:2654731
3636:2803042
3552:6673447
3474:3058259
3425:6729542
3278:6758802
3246:9614245
3237:6792696
3188:6817686
3167:Bibcode
3090:3224674
3041:4999418
2992:9925750
2908:1571615
2859:1574197
2769:9879039
2716:3589707
2660:1279673
2620:8710940
2588:Bibcode
2561:2038246
2483:9419374
2451:Bibcode
2416:9491897
2291:3058259
2123:Ensembl
2102:Ensembl
1959:PF02072
1848:ESSENCE
1791:glucose
1783:ghrelin
1740:CB1–OX1
1674:glucose
1635:alcohol
1618:glucose
1609:Ghrelin
1581:neurons
1572:in the
1528:canine
1349:GenBank
1301:orexins
1253:peptide
1230:, from
1210:peptide
1202:neurons
1171:arousal
1165:, is a
922:UniProt
877:Ensembl
816:Species
795:QuickGO
634:synapse
446:putamen
379:pattern
237:17q21.2
137:1202306
105:Aliases
6907:Orexin
6897:E-2086
6882:AEX-19
6744:Orexin
6739:AEX-24
6734:AEX-19
6432:Kinins
6365:Others
6083:Sugars
5927:(MeSH)
5903:
5895:
5852:
5842:
5800:
5790:
5759:
5749:
5578:
5568:
5527:
5517:
5476:
5466:
5425:
5415:
5374:
5366:
5331:
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