328:
31:
362:, a neuroprotective and bronchodilator drug used mainly in the treatment of asthma and stroke. It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor, depending on the dose.
1020:
1577:
Bobon D, Breulet M, Gerard-Vandenhove MA, Guiot-Goffioul F, Plomteux G, Sastre-y-Hernandez M, Schratzer M, Troisfontaines B, von
Frenckell R, Wachtel H (1988). "Is phosphodiesterase inhibition a new mechanism of antidepressant action? A double blind double-dummy study between rolipram and desipramine
467:
reported that researchers at their institution had discovered a link between elevated levels of PDE4 (and therefore decreased levels of cAMP) in sleep deprived mice. Treatment with a PDE4 inhibitor raised the deficient cAMP levels and restored some functionality to hippocampus-based memory functions.
73:
The different forms or subtypes of phosphodiesterase were initially isolated from rat brains in the early 1970s and were soon afterward shown to be selectively inhibited in the brain and in other tissues by a variety of drugs. The potential for selective phosphodiesterase inhibitors as therapeutic
2030:
Inhibitory
Mechanism of Papaverine on Carbachol-Induced Contraction in Bovine Trachea; Takeharu Kaneda1,*, Yukako Takeuchi1, Hirozumi Matsui1, Kazumasa Shimizu1, Norimoto Urakawa1,and Shinjiro Nakajyo, Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University;
1806:
Guerreiro, Serge; Toulorge, Damien; Hirsch, Etienne; Marien, Marc; Sokoloff, Pierre; Michel, Patrick P. (October 2008). "Paraxanthine, the primary metabolite of caffeine, provides protection against dopaminergic cell death via stimulation of ryanodine receptor channels".
1770:
Redondo, M.; Zarruk, JG.; Ceballos, P.; Pérez, DI.; Pérez, C.; Perez-Castillo, A.; Moro, MA.; Brea, J.; et al. (Jan 2012). "Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model".
2078:
Effects of phosphodiesterase 10 inhibition on striatal cyclic AMP and peripheral physiology in rats; An
Torremans, Abdellah Ahnaou, An Van Hemelrijck, Roel Straetemans, Helena Geys, Greet Vanhoof, Theo F. Meert, and Wilhelmus H. Drinkenburg;
1511:
Yu MC, Chen JH, Lai CY, Han CY, Ko WC (2009). "Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1–5, displaced -rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia".
65:(cGMP) by the respective PDE subtype(s). The ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, the actions in the heart, and lungs being some of the first to find a therapeutic use.
1135:
Shamim MT, Ukena D, Padgett WL, Daly JW (June 1989). "Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di-, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions".
993:
1875:
Orrú, Marco; Guitart, Xavier; Karcz-Kubicha, Marzena; Solinas, Marcello; Justinova, Zuzana; Barodia, Sandeep Kumar; Zanoveli, Janaina; Cortes, Antoni; Lluis, Carme; Casado, Vicent; Moeller, F. Gerard (April 2013).
1547:
560:(84% in humans), is another cGMP-specific phosphodiesterase inhibitor which inhibits PDE9, a cGMP preferring phosphodiesterase. PDE9 is expressed as high as PDE5 in the corpus cavernosum.
1000:, Sunshine A, Laska EM, Siegel CE, "ANALGESIC AND ANTI-INFLAMMATORY COMPOSITIONS COMPRISING XANTHINES AND METHODS OF USING SAME", granted 1989-03-22, assigned to RICHARDSON-VICKS, INC.
638:
Uzunov P.; Weiss B. (1972). "Separation of multiple molecular forms of cyclic adenosine 3',5'-monophosphate phosphodiesterase in rat cerebellum by polyacrylamide gel electrophoresis".
2144:
133:, a drug that has the potential to enhance circulation and may have applicability in treatment of diabetes, fibrotic disorders, peripheral nerve damage, and microvascular injuries
432:
PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells. PDE4 inhibitors have proven potential as anti-inflammatory drugs, especially in inflammatory
990:
1713:
Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, Huang T, Brown KM, Li XY, Descalzi G, Kim SS, Chen T, Shang YZ, Zhuo M, Houslay MD, Abel T (2009).
1386:
Baraldi PG, Tabrizi MA, Gessi S, Borea PA (January 2008). "Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility".
1555:
1098:"Caffeine and theophylline analogues: correlation of behavioral effects with activity as adenosine receptor antagonists and as phosphodiesterase inhibitors"
3010:
2169:
1034:
Daly JW, Padgett WL, Shamim MT (July 1986). "Analogues of caffeine and theophylline: effect of structural alterations on affinity at adenosine receptors".
2137:
2112:
858:
Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages".
1621:
Maxwell CR, Kanes SJ, Abel T, Siegel SJ (2004). "Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications".
1343:
González MP, Terán C, Teijeira M (May 2008). "Search for new antagonist ligands for adenosine receptors from QSAR point of view. How close are we?".
2217:
1935:"Phosphodiesterase-9 (PDE9) inhibition with BAY 73-6691 increases corpus cavernosum relaxations mediated by nitric oxide–cyclic GMP pathway in mice"
3433:
2130:
441:
1423:"Development of acute myocardial infarction in a young female patient with essential thrombocythemia treated with anagrelide: a case report"
87:
811:"Insights into the Regulation of TNF-α Production in Human Mononuclear Cells: The Effects of Non-Specific Phosphodiesterase Inhibition"
3344:
3188:
3147:
2827:
1212:
1210:
Ukena D, Schudt C, Sybrecht GW (February 1993). "Adenosine receptor-blocking xanthines as inhibitors of phosphodiesterase isozymes".
3296:
3113:
1548:"Powered by Skipta technology, PharmacistSociety.com is the social network for verified Pharmacists to communicate and collaborate"
3305:
3219:
3003:
2044:
Pöch, G.; Kukovetz, W.R. (1971). "Papaverine - induced inhibition of phosphodiesterase activity in various mammalian tissues".
3265:
3172:
164:
62:
58:
3359:
3193:
168:
3392:
3384:
2978:
727:
Weiss B.; Hait W.N. (1977). "Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents".
160:
673:
Weiss B (1975). "Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase".
3288:
3278:
3201:
3105:
2908:
700:
Fertel R, Weiss B (1976). "Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung".
3142:
3084:
3047:
2996:
464:
284:
75:
3408:
3231:
3097:
303:
1069:
Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists".
937:
Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists".
452:
and other inflammatory signals, and inhibit the production of reactive oxygen species. PDE4 inhibitors may have
3364:
3226:
3339:
3317:
3283:
3042:
2088:
507:
413:
390:, indicated for people with severe COPD to prevent symptoms such as coughing and excess mucus from worsening
603:
Thompson WJ, Appleman MM (1971). "Multiple cyclic nucleotide phosphodiesterase activities from rat brain".
3300:
3270:
3236:
3209:
3121:
3037:
2822:
515:
3349:
1933:
da Silva, F H; Pereira, M N; Franco-Penteado, C F; De Nucci, G; Antunes, E; Claudino, M A (March 2013).
327:
2661:
1726:
511:
198:
But different analogues show varying potency at the numerous subtypes, and a wide range of synthetic
1878:"Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans"
3214:
3129:
417:
347:
2958:
2523:
2423:
2413:
2383:
2320:
2250:
202:(some nonmethylated) have been developed in the search for compounds with greater selectivity for
3052:
2737:
2631:
2388:
1840:
1646:
1603:
1368:
1325:
207:
191:
2933:
2923:
2760:
2621:
2568:
2563:
2548:
2533:
2528:
2513:
2488:
2483:
2478:
2468:
2428:
2310:
2295:
2260:
2202:
578:, has been reported to act as a PDE10 inhibitor. PDE10A is almost exclusively expressed in the
2775:
2611:
3322:
2953:
2656:
2558:
2508:
2403:
2285:
2106:
2061:
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1964:
1956:
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1832:
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1788:
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1638:
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1452:
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1360:
1317:
1268:
1229:
1192:
1153:
1117:
1078:
1051:
946:
919:
875:
840:
788:
744:
709:
682:
655:
620:
433:
203:
180:
50:
2796:
2398:
3057:
3023:
2053:
2003:
1995:
1946:
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1889:
1816:
1780:
1742:
1734:
1685:
1677:
1630:
1587:
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1483:
1442:
1434:
1395:
1352:
1307:
1299:
1260:
1221:
1184:
1145:
1109:
1043:
973:
909:
867:
830:
822:
778:
736:
647:
612:
54:
17:
1470:
de Visser YP, Walther FJ, Laghmani EH, van
Wijngaarden S, Nieuwland K, Wagenaar GT (2008).
3327:
3134:
2867:
2676:
1666:"Rolipram: A specific phosphodiesterase 4 inhibitor with potential antipsychotic activity"
1472:"Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury"
997:
280:
184:
2032:
1730:
1312:
740:
3180:
3167:
3074:
2862:
2636:
2616:
2588:
2360:
2227:
2008:
1984:"Evaluating the antipsychotic profile of the preferential PDE10A inhibitor, papaverine"
1983:
1910:
1877:
1747:
1714:
1690:
1681:
1665:
1634:
1447:
1422:
835:
810:
477:
453:
336:
288:
262:
145:
130:
1264:
3427:
3310:
2943:
2903:
2812:
2596:
2057:
1893:
1225:
1113:
651:
457:
172:
122:(3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research
114:
1844:
1650:
1372:
826:
3019:
2938:
2877:
2842:
2832:
2742:
2498:
2438:
2280:
1607:
1329:
553:
525:
521:
342:
141:
125:
30:
2988:
78:
and Hait. This prediction meanwhile has proved to be true in a variety of fields.
1784:
1525:
1015:
871:
384:, used to alleviate renal colic pain, also to hasten cervical dilatation in labor
3157:
2918:
2913:
2872:
2837:
2765:
2732:
2646:
2578:
2538:
2518:
2473:
2433:
2418:
2350:
2345:
2265:
2255:
2197:
2179:
542:
425:
399:
387:
381:
365:
312:
is FDA approved for veterinary use in the treatment of heart failure in animals.
241:
176:
136:
2122:
1421:
Lim YH, Lee YY, Kim JH, Shin J, Lee JU, Kim KS, Kim SK, Kim JH, Lim HK (2010).
914:
897:
545:
type PDE7 inhibitor to be potent anti-inflammatory and neuroprotective agents.
2928:
2770:
2696:
2671:
2601:
2503:
2448:
2408:
2373:
2368:
2340:
2335:
2315:
2270:
2245:
1999:
1488:
1471:
1438:
1303:
583:
568:
491:
483:
393:
309:
299:
294:
43:
1960:
1901:
1828:
3250:
2948:
2882:
2847:
2780:
2714:
2686:
2666:
2641:
2463:
2443:
2325:
2305:
2300:
2275:
2235:
2174:
1858:
783:
766:
506:, which is cGMP-specific and responsible for the degradation of cGMP in the
487:
409:
359:
276:
272:
152:
109:
98:
2017:
1968:
1919:
1836:
1820:
1792:
1756:
1699:
1642:
1533:
1497:
1456:
1407:
1364:
1321:
1272:
1173:"Caffeine analogs: structure-activity relationships at adenosine receptors"
923:
844:
792:
524:
also inhibits PDE5. This results in added benefit when given together with
2065:
1599:
1233:
1196:
1157:
1121:
1082:
1055:
964:
MacCorquodale, DW (July 1929). "The
Synthesis of Some Alkylxanthines1,2".
950:
879:
659:
624:
582:
and subsequent increase in cAMP and cGMP after PDE10A inhibition (e.g. by
2963:
2898:
2857:
2817:
2691:
2606:
2543:
2493:
2453:
2378:
2240:
2212:
1982:
Weber M, Breier M, Ko D, Thangaraj N, Marzan DE, Swerdlow NR (May 2009).
1951:
1934:
713:
686:
579:
575:
557:
514:, as well as having some other medical applications such as treatment of
510:. These phosphodiesterase inhibitors are used primarily as remedies for
499:
495:
449:
445:
405:
371:
353:
268:
247:
199:
105:
1738:
1149:
1047:
977:
748:
616:
2651:
2626:
2553:
2458:
2393:
2330:
1591:
1399:
1356:
1188:
586:) is "a novel therapeutic avenue in the discovery of antipsychotics".
3089:
2681:
2573:
2290:
1664:
Kanes SJ, Tokarczyk J, Siegel SJ, Bilker W, Abel T, Kelly MP (2006).
898:"Leukotrienes: underappreciated mediators of innate immune responses"
529:
437:
421:
47:
1287:
1248:
1172:
1097:
252:
PDP (9-(6-Phenyl-2-oxohex-3-yl)-2-(3,4-dimethoxybenzyl)-purin-6-one)
3374:
2790:
2752:
572:
375:
326:
29:
2081:
2852:
2724:
2706:
2207:
2189:
2161:
503:
316:
219:
119:
53:(PDE), thereby preventing the inactivation of the intracellular
2992:
2126:
809:
Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (2008).
2804:
319:
is sometimes referred to as cGMP-inhibited phosphodiesterase.
1715:"Sleep deprivation impairs cAMP signaling in the hippocampus"
1010:
Constantin
Koulbanis, Claude Bouillon, Patrick Darmenton,
896:
Peters-Golden M, Canetti C, Mancuso P, Coffey MJ (2005).
374:, supplement extracted from peanuts that also possesses
356:, used as investigative tool in pharmacological research
244:(2--7--4-phenylbutyl]-5-methyl-imidazotriazin-4(1H)-one)
2033:
http://www.jstage.jst.go.jp/article/jphs/98/3/275/_pdf
1578:
in hospitalized major and/or endogenous depressives".
46:
that blocks one or more of the five subtypes of the
3401:
3373:
3249:
3156:
3073:
3066:
3030:
2891:
2803:
2789:
2751:
2723:
2705:
2587:
2359:
2226:
2188:
2160:
891:
889:
396:, used to treat psoriasis and psoriatic arthritis.
1096:Choi OH, Shamim MT, Padgett WL, Daly JW (1988).
1012:"Cosmetic compositions having a slimming action"
279:are used clinically for short-term treatment of
456:effects and have also been proposed for use as
771:The Journal of Allergy and Clinical Immunology
760:
758:
3004:
2138:
1171:Daly JW, Hide I, Müller CE, Shamim M (1991).
8:
1071:Progress in Clinical and Biological Research
1939:International Journal of Impotence Research
804:
802:
3070:
3011:
2997:
2989:
2145:
2131:
2123:
1018:, granted 1981-09-04 , assigned to L'Oreal
2007:
1950:
1909:
1746:
1689:
1487:
1446:
1311:
913:
834:
782:
74:agents was predicted as early as 1977 by
966:Journal of the American Chemical Society
368:, a more potent inhibitor than rolipram.
1253:Journal of the Autonomic Nervous System
595:
424:positive allosteric modulator, used as
2111:: CS1 maint: archived copy as title (
2104:
767:"Cyclic nucleotide phosphodiesterases"
412:alkaloid, low-potency PDE4 inhibitor,
1288:"Caffeine analogs: biomedical impact"
7:
1292:Cellular and Molecular Life Sciences
88:List of phosphodiesterase inhibitors
741:10.1146/annurev.pa.17.040177.002301
1682:10.1016/j.neuroscience.2006.09.026
1635:10.1016/j.neuroscience.2004.07.038
1249:"Alkylxanthines as research tools"
402:, used to treat atopic dermatitis.
25:
1894:10.1016/j.neuropharm.2012.11.029
2094:from the original on 2011-10-07
827:10.1590/S1807-59322008000300006
448:. They suppress the release of
1580:Eur Arch Psychiatry Neurol Sci
1138:Journal of Medicinal Chemistry
1036:Journal of Medicinal Chemistry
428:in Eastern Europe and Iceland.
63:cyclic guanosine monophosphate
59:cyclic adenosine monophosphate
1:
2979:Receptor/signaling modulators
1265:10.1016/S0165-1838(00)00110-7
860:Am. J. Respir. Crit. Care Med
729:Annu. Rev. Pharmacol. Toxicol
3434:Phosphodiesterase inhibitors
2154:Phosphodiesterase inhibitors
2058:10.1016/0024-3205(71)90086-5
1785:10.1016/j.ejmech.2011.10.040
1552:pharmacistsociety.skipta.com
1526:10.1016/j.ejphar.2009.10.031
1226:10.1016/0006-2952(93)90168-V
1114:10.1016/0024-3205(88)90517-6
872:10.1164/ajrccm.159.2.9804085
652:10.1016/0005-2744(72)90060-5
345:, an alkaloid from the herb
302:is used in the treatment of
163:, which raise intracellular
161:phosphodiesterase inhibitors
18:Phosphodiesterase inhibitors
1016:US patent 4288433
93:Nonselective PDE inhibitors
40:phosphodiesterase inhibitor
3450:
3189:Dihydropteroate synthetase
3048:Non-competitive inhibition
1345:Medicinal Research Reviews
915:10.4049/jimmunol.174.2.589
564:PDE10 selective inhibitors
541:Recent studies have shown
475:
465:University of Pennsylvania
334:
260:
85:
3409:Steroidogenesis inhibitor
2972:
2000:10.1007/s00213-008-1419-x
1489:10.1183/09031936.00071307
1439:10.5045/kjh.2010.45.2.136
1304:10.1007/s00018-007-7051-9
556:, the main metabolite of
549:PDE9 selective inhibitors
537:PDE7 selective inhibitors
472:PDE5 selective inhibitors
463:On October 26, 2009, the
323:PDE4 selective inhibitors
304:intermittent claudication
287:stimulation and increase
257:PDE3 selective inhibitors
214:PDE2 selective inhibitors
159:competitive nonselective
3345:Matrix metalloproteinase
3148:Ribonucleotide reductase
3043:Uncompetitive inhibition
1213:Biochemical Pharmacology
204:phosphodiesterase enzyme
3114:Dihydrofolate reductase
1286:Daly JW (August 2007).
784:10.1067/mai.2001.119555
414:calcium channel blocker
3210:Nucleotidyltransferase
3038:Competitive inhibition
2823:Choline theophyllinate
1821:10.1124/mol.108.048207
1809:Molecular Pharmacology
640:Biochim. Biophys. Acta
516:pulmonary hypertension
332:
35:
3220:Reverse transcriptase
2241:Amrinone (inamrinone)
1247:Daly JW (July 2000).
902:Journal of Immunology
330:
283:. These drugs mimic
33:
3266:Acetylcholinesterase
3173:Thymidylate synthase
1952:10.1038/ijir.2012.35
991:WO patent 1985002540
765:Essayan DM. (2001).
675:Adv. Cycl. Nucl. Res
512:erectile dysfunction
502:selectively inhibit
200:xanthine derivatives
3360:Histone deacetylase
3194:Farnesyltransferase
1739:10.1038/nature08488
1731:2009Natur.461.1122V
1725:(7267): 1122–1125.
1150:10.1021/jm00126a014
1048:10.1021/jm00157a035
978:10.1021/ja01382a042
815:Clinics (Sao Paulo)
617:10.1021/bi00778a018
418:dopamine antagonist
348:Sceletium tortuosum
181:reduce inflammation
34:Phosphodiesterase-5
3393:Carbonic anhydrase
3385:Dopa decarboxylase
3053:Suicide inhibition
1988:Psychopharmacology
1592:10.1007/BF00381071
996:2011-08-05 at the
939:Prog Clin Biol Res
434:pulmonary diseases
333:
208:adenosine receptor
192:adenosine receptor
36:
3421:
3420:
3417:
3416:
3289:Alpha-glucosidase
3279:Polygalacturonase
3261:Phosphodiesterase
3202:GABA transaminase
3106:Monoamine oxidase
3090:HMG-CoA reductase
3024:enzyme inhibition
2986:
2985:
2657:Nitrosoprodenafil
1882:Neuropharmacology
1400:10.1021/cr0682195
1357:10.1002/med.20108
1189:10.1159/000138813
508:corpus cavernosum
173:inhibit TNF-alpha
101:and derivatives:
55:second messengers
51:phosphodiesterase
16:(Redirected from
3441:
3143:Xanthine oxidase
3085:Aldose reductase
3071:
3058:Mixed inhibition
3013:
3006:
2999:
2990:
2147:
2140:
2133:
2124:
2117:
2116:
2110:
2102:
2100:
2099:
2093:
2086:
2076:
2070:
2069:
2041:
2035:
2028:
2022:
2021:
2011:
1979:
1973:
1972:
1954:
1930:
1924:
1923:
1913:
1872:
1866:
1865:
1863:
1855:
1849:
1848:
1803:
1797:
1796:
1767:
1761:
1760:
1750:
1710:
1704:
1703:
1693:
1661:
1655:
1654:
1618:
1612:
1611:
1574:
1568:
1567:
1565:
1563:
1558:on 19 April 2012
1554:. Archived from
1544:
1538:
1537:
1508:
1502:
1501:
1491:
1467:
1461:
1460:
1450:
1427:Korean J Hematol
1418:
1412:
1411:
1388:Chemical Reviews
1383:
1377:
1376:
1340:
1334:
1333:
1315:
1283:
1277:
1276:
1244:
1238:
1237:
1207:
1201:
1200:
1168:
1162:
1161:
1132:
1126:
1125:
1093:
1087:
1086:
1066:
1060:
1059:
1031:
1025:
1024:
1023:
1019:
1007:
1001:
988:
982:
981:
972:(7): 2245–2251.
961:
955:
954:
934:
928:
927:
917:
893:
884:
883:
855:
849:
848:
838:
806:
797:
796:
786:
762:
753:
752:
724:
718:
717:
697:
691:
690:
670:
664:
663:
635:
629:
628:
600:
494:, and the newer
21:
3449:
3448:
3444:
3443:
3442:
3440:
3439:
3438:
3424:
3423:
3422:
3413:
3397:
3369:
3245:
3232:Tyrosine kinase
3152:
3062:
3026:
3017:
2987:
2982:
2968:
2887:
2868:Propentofylline
2799:
2785:
2747:
2719:
2701:
2677:Sulfoaildenafil
2662:Norcarbodenafil
2583:
2355:
2222:
2184:
2156:
2151:
2121:
2120:
2103:
2097:
2095:
2091:
2084:
2082:"Archived copy"
2080:
2077:
2073:
2043:
2042:
2038:
2029:
2025:
1981:
1980:
1976:
1932:
1931:
1927:
1874:
1873:
1869:
1861:
1857:
1856:
1852:
1805:
1804:
1800:
1769:
1768:
1764:
1712:
1711:
1707:
1663:
1662:
1658:
1620:
1619:
1615:
1576:
1575:
1571:
1561:
1559:
1546:
1545:
1541:
1520:(1–3): 269–75.
1514:Eur J Pharmacol
1510:
1509:
1505:
1469:
1468:
1464:
1420:
1419:
1415:
1385:
1384:
1380:
1342:
1341:
1337:
1298:(16): 2153–69.
1285:
1284:
1280:
1246:
1245:
1241:
1209:
1208:
1204:
1170:
1169:
1165:
1134:
1133:
1129:
1095:
1094:
1090:
1068:
1067:
1063:
1033:
1032:
1028:
1021:
1009:
1008:
1004:
998:Wayback Machine
989:
985:
963:
962:
958:
936:
935:
931:
895:
894:
887:
857:
856:
852:
808:
807:
800:
764:
763:
756:
726:
725:
721:
699:
698:
694:
672:
671:
667:
637:
636:
632:
602:
601:
597:
592:
566:
551:
539:
480:
474:
339:
331:PDE4 inhibitors
325:
281:cardiac failure
265:
259:
216:
185:innate immunity
179:synthesis, and
95:
90:
84:
71:
28:
23:
22:
15:
12:
11:
5:
3447:
3445:
3437:
3436:
3426:
3425:
3419:
3418:
3415:
3414:
3412:
3411:
3405:
3403:
3399:
3398:
3396:
3395:
3388:
3387:
3380:
3378:
3371:
3370:
3368:
3367:
3365:Beta-lactamase
3362:
3355:
3354:
3353:
3352:
3347:
3342:
3332:
3331:
3330:
3325:
3315:
3314:
3313:
3308:
3292:
3291:
3286:
3281:
3274:
3273:
3268:
3263:
3256:
3254:
3247:
3246:
3244:
3243:
3242:
3241:
3240:
3239:
3227:Protein kinase
3224:
3223:
3222:
3217:
3205:
3204:
3197:
3196:
3191:
3184:
3183:
3176:
3175:
3170:
3163:
3161:
3154:
3153:
3151:
3150:
3145:
3138:
3137:
3132:
3125:
3124:
3117:
3116:
3109:
3108:
3101:
3100:
3093:
3092:
3087:
3080:
3078:
3075:Oxidoreductase
3068:
3064:
3063:
3061:
3060:
3055:
3050:
3045:
3040:
3034:
3032:
3028:
3027:
3018:
3016:
3015:
3008:
3001:
2993:
2984:
2983:
2973:
2970:
2969:
2967:
2966:
2961:
2956:
2951:
2946:
2941:
2936:
2931:
2926:
2921:
2916:
2911:
2906:
2901:
2895:
2893:
2889:
2888:
2886:
2885:
2880:
2875:
2870:
2865:
2863:Pentoxifylline
2860:
2855:
2850:
2845:
2840:
2835:
2830:
2825:
2820:
2815:
2809:
2807:
2801:
2800:
2795:
2793:
2787:
2786:
2784:
2783:
2778:
2773:
2768:
2763:
2757:
2755:
2749:
2748:
2746:
2745:
2740:
2735:
2729:
2727:
2721:
2720:
2718:
2717:
2711:
2709:
2703:
2702:
2700:
2699:
2694:
2689:
2684:
2679:
2674:
2669:
2664:
2659:
2654:
2649:
2644:
2639:
2637:Homosildenafil
2634:
2629:
2624:
2619:
2617:Benzamidenafil
2614:
2609:
2604:
2599:
2593:
2591:
2585:
2584:
2582:
2581:
2576:
2571:
2566:
2561:
2556:
2551:
2546:
2541:
2536:
2531:
2526:
2521:
2516:
2511:
2506:
2501:
2496:
2491:
2486:
2481:
2476:
2471:
2466:
2461:
2456:
2451:
2446:
2441:
2436:
2431:
2426:
2421:
2416:
2411:
2406:
2401:
2396:
2391:
2386:
2381:
2376:
2371:
2365:
2363:
2357:
2356:
2354:
2353:
2348:
2343:
2338:
2333:
2328:
2323:
2318:
2313:
2308:
2303:
2298:
2293:
2288:
2283:
2278:
2273:
2268:
2263:
2258:
2253:
2248:
2243:
2238:
2232:
2230:
2224:
2223:
2221:
2220:
2215:
2210:
2205:
2200:
2194:
2192:
2186:
2185:
2183:
2182:
2177:
2172:
2166:
2164:
2158:
2157:
2152:
2150:
2149:
2142:
2135:
2127:
2119:
2118:
2071:
2052:(3): 133–144.
2036:
2023:
1974:
1925:
1867:
1859:"Paraxanthine"
1850:
1815:(4): 980–989.
1798:
1773:Eur J Med Chem
1762:
1705:
1656:
1613:
1569:
1539:
1503:
1482:(3): 633–644.
1462:
1413:
1378:
1335:
1278:
1259:(1–3): 44–52.
1239:
1202:
1163:
1127:
1088:
1061:
1026:
1002:
983:
956:
929:
885:
850:
798:
754:
719:
708:(4): 678–687.
702:Mol. Pharmacol
692:
665:
646:(1): 220–226.
630:
594:
593:
591:
588:
565:
562:
550:
547:
538:
535:
534:
533:
519:
478:PDE5 inhibitor
476:Main article:
473:
470:
458:antipsychotics
454:antidepressive
430:
429:
403:
397:
391:
385:
379:
369:
363:
357:
351:
337:PDE4 inhibitor
335:Main article:
324:
321:
314:
313:
307:
297:
292:
289:cardiac output
263:PDE3 inhibitor
261:Main article:
258:
255:
254:
253:
250:
245:
239:
215:
212:
196:
195:
188:
149:
148:
146:bronchodilator
139:
134:
131:pentoxifylline
128:
123:
117:
112:
94:
91:
83:
82:Classification
80:
70:
67:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
3446:
3435:
3432:
3431:
3429:
3410:
3407:
3406:
3404:
3402:Miscellaneous
3400:
3394:
3390:
3389:
3386:
3382:
3381:
3379:
3376:
3372:
3366:
3363:
3361:
3357:
3356:
3351:
3348:
3346:
3343:
3341:
3340:Enkephalinase
3338:
3337:
3336:
3333:
3329:
3326:
3324:
3321:
3320:
3319:
3318:Endopeptidase
3316:
3312:
3309:
3307:
3304:
3303:
3302:
3298:
3294:
3293:
3290:
3287:
3285:
3284:Neuraminidase
3282:
3280:
3276:
3275:
3272:
3269:
3267:
3264:
3262:
3258:
3257:
3255:
3252:
3248:
3238:
3235:
3234:
3233:
3230:
3229:
3228:
3225:
3221:
3218:
3216:
3213:
3212:
3211:
3207:
3206:
3203:
3199:
3198:
3195:
3192:
3190:
3186:
3185:
3182:
3178:
3177:
3174:
3171:
3169:
3165:
3164:
3162:
3159:
3155:
3149:
3146:
3144:
3140:
3139:
3136:
3133:
3131:
3127:
3126:
3123:
3119:
3118:
3115:
3111:
3110:
3107:
3103:
3102:
3099:
3095:
3094:
3091:
3088:
3086:
3082:
3081:
3079:
3076:
3072:
3069:
3065:
3059:
3056:
3054:
3051:
3049:
3046:
3044:
3041:
3039:
3036:
3035:
3033:
3029:
3025:
3021:
3014:
3009:
3007:
3002:
3000:
2995:
2994:
2991:
2981:
2980:
2977:
2971:
2965:
2962:
2960:
2957:
2955:
2952:
2950:
2947:
2945:
2944:Proxyphylline
2942:
2940:
2937:
2935:
2932:
2930:
2927:
2925:
2922:
2920:
2917:
2915:
2912:
2910:
2907:
2905:
2904:Diprophylline
2902:
2900:
2897:
2896:
2894:
2890:
2884:
2881:
2879:
2876:
2874:
2871:
2869:
2866:
2864:
2861:
2859:
2856:
2854:
2851:
2849:
2846:
2844:
2841:
2839:
2836:
2834:
2831:
2829:
2826:
2824:
2821:
2819:
2816:
2814:
2813:Aminophylline
2811:
2810:
2808:
2806:
2805:Non-selective
2802:
2798:
2794:
2792:
2788:
2782:
2779:
2777:
2774:
2772:
2769:
2767:
2764:
2762:
2759:
2758:
2756:
2754:
2750:
2744:
2741:
2739:
2736:
2734:
2731:
2730:
2728:
2726:
2722:
2716:
2713:
2712:
2710:
2708:
2704:
2698:
2695:
2693:
2690:
2688:
2685:
2683:
2680:
2678:
2675:
2673:
2670:
2668:
2665:
2663:
2660:
2658:
2655:
2653:
2650:
2648:
2645:
2643:
2640:
2638:
2635:
2633:
2630:
2628:
2625:
2623:
2620:
2618:
2615:
2613:
2610:
2608:
2605:
2603:
2600:
2598:
2597:Acetildenafil
2595:
2594:
2592:
2590:
2586:
2580:
2577:
2575:
2572:
2570:
2567:
2565:
2562:
2560:
2557:
2555:
2552:
2550:
2547:
2545:
2542:
2540:
2537:
2535:
2532:
2530:
2527:
2525:
2522:
2520:
2517:
2515:
2512:
2510:
2507:
2505:
2502:
2500:
2497:
2495:
2492:
2490:
2487:
2485:
2482:
2480:
2477:
2475:
2472:
2470:
2467:
2465:
2462:
2460:
2457:
2455:
2452:
2450:
2447:
2445:
2442:
2440:
2437:
2435:
2432:
2430:
2427:
2425:
2422:
2420:
2417:
2415:
2412:
2410:
2407:
2405:
2402:
2400:
2397:
2395:
2392:
2390:
2387:
2385:
2382:
2380:
2377:
2375:
2372:
2370:
2367:
2366:
2364:
2362:
2358:
2352:
2349:
2347:
2344:
2342:
2339:
2337:
2334:
2332:
2329:
2327:
2324:
2322:
2319:
2317:
2314:
2312:
2309:
2307:
2304:
2302:
2299:
2297:
2294:
2292:
2289:
2287:
2284:
2282:
2279:
2277:
2274:
2272:
2269:
2267:
2264:
2262:
2259:
2257:
2254:
2252:
2249:
2247:
2244:
2242:
2239:
2237:
2234:
2233:
2231:
2229:
2225:
2219:
2216:
2214:
2211:
2209:
2206:
2204:
2201:
2199:
2196:
2195:
2193:
2191:
2187:
2181:
2178:
2176:
2173:
2171:
2168:
2167:
2165:
2163:
2159:
2155:
2148:
2143:
2141:
2136:
2134:
2129:
2128:
2125:
2114:
2108:
2090:
2083:
2075:
2072:
2067:
2063:
2059:
2055:
2051:
2047:
2046:Life Sciences
2040:
2037:
2034:
2027:
2024:
2019:
2015:
2010:
2005:
2001:
1997:
1994:(4): 723–35.
1993:
1989:
1985:
1978:
1975:
1970:
1966:
1962:
1958:
1953:
1948:
1944:
1940:
1936:
1929:
1926:
1921:
1917:
1912:
1907:
1903:
1899:
1895:
1891:
1887:
1883:
1879:
1871:
1868:
1860:
1854:
1851:
1846:
1842:
1838:
1834:
1830:
1826:
1822:
1818:
1814:
1810:
1802:
1799:
1794:
1790:
1786:
1782:
1779:(1): 175–85.
1778:
1774:
1766:
1763:
1758:
1754:
1749:
1744:
1740:
1736:
1732:
1728:
1724:
1720:
1716:
1709:
1706:
1701:
1697:
1692:
1687:
1683:
1679:
1676:(1): 239–46.
1675:
1671:
1667:
1660:
1657:
1652:
1648:
1644:
1640:
1636:
1632:
1628:
1624:
1617:
1614:
1609:
1605:
1601:
1597:
1593:
1589:
1585:
1581:
1573:
1570:
1557:
1553:
1549:
1543:
1540:
1535:
1531:
1527:
1523:
1519:
1515:
1507:
1504:
1499:
1495:
1490:
1485:
1481:
1477:
1473:
1466:
1463:
1458:
1454:
1449:
1444:
1440:
1436:
1432:
1428:
1424:
1417:
1414:
1409:
1405:
1401:
1397:
1394:(1): 238–63.
1393:
1389:
1382:
1379:
1374:
1370:
1366:
1362:
1358:
1354:
1351:(3): 329–71.
1350:
1346:
1339:
1336:
1331:
1327:
1323:
1319:
1314:
1309:
1305:
1301:
1297:
1293:
1289:
1282:
1279:
1274:
1270:
1266:
1262:
1258:
1254:
1250:
1243:
1240:
1235:
1231:
1227:
1223:
1220:(4): 847–51.
1219:
1215:
1214:
1206:
1203:
1198:
1194:
1190:
1186:
1183:(6): 309–21.
1182:
1178:
1174:
1167:
1164:
1159:
1155:
1151:
1147:
1144:(6): 1231–7.
1143:
1139:
1131:
1128:
1123:
1119:
1115:
1111:
1108:(5): 387–98.
1107:
1103:
1102:Life Sciences
1099:
1092:
1089:
1084:
1080:
1076:
1072:
1065:
1062:
1057:
1053:
1049:
1045:
1042:(7): 1305–8.
1041:
1037:
1030:
1027:
1017:
1013:
1006:
1003:
999:
995:
992:
987:
984:
979:
975:
971:
967:
960:
957:
952:
948:
944:
940:
933:
930:
925:
921:
916:
911:
908:(2): 589–94.
907:
903:
899:
892:
890:
886:
881:
877:
873:
869:
866:(2): 508–11.
865:
861:
854:
851:
846:
842:
837:
832:
828:
824:
820:
816:
812:
805:
803:
799:
794:
790:
785:
780:
777:(5): 671–80.
776:
772:
768:
761:
759:
755:
750:
746:
742:
738:
734:
730:
723:
720:
715:
711:
707:
703:
696:
693:
688:
684:
680:
676:
669:
666:
661:
657:
653:
649:
645:
641:
634:
631:
626:
622:
618:
614:
610:
606:
599:
596:
589:
587:
585:
581:
577:
574:
570:
563:
561:
559:
555:
548:
546:
544:
536:
531:
527:
523:
520:
517:
513:
509:
505:
501:
497:
493:
489:
485:
482:
481:
479:
471:
469:
466:
461:
459:
455:
451:
447:
443:
439:
435:
427:
423:
419:
415:
411:
407:
404:
401:
398:
395:
392:
389:
386:
383:
380:
377:
373:
370:
367:
364:
361:
358:
355:
352:
350:
349:
344:
341:
340:
338:
329:
322:
320:
318:
311:
308:
305:
301:
298:
296:
293:
290:
286:
282:
278:
274:
270:
267:
266:
264:
256:
251:
249:
246:
243:
240:
237:
233:
229:
225:
221:
218:
217:
213:
211:
209:
205:
201:
193:
190:nonselective
189:
186:
182:
178:
174:
170:
166:
162:
158:
157:
156:
154:
147:
143:
140:
138:
135:
132:
129:
127:
124:
121:
118:
116:
115:aminophylline
113:
111:
107:
104:
103:
102:
100:
92:
89:
81:
79:
77:
68:
66:
64:
60:
56:
52:
49:
45:
41:
32:
19:
3334:
3301:Exopeptidase
3271:Ribonuclease
3260:
3237:Janus kinase
3122:Lipoxygenase
3098:5α-Reductase
3020:Pharmacology
2975:
2974:
2959:Tolafentrine
2939:Pentifylline
2878:Theophylline
2843:Enprofylline
2833:Dipyridamole
2743:Paraxanthine
2524:Pumafentrine
2499:Mesembrenone
2439:Ensifentrine
2424:Denbutylline
2414:Cipamfylline
2384:Benafentrine
2321:Pumafentrine
2281:Ensifentrine
2251:Benafentrine
2153:
2096:. Retrieved
2074:
2049:
2045:
2039:
2026:
1991:
1987:
1977:
1945:(2): 69–73.
1942:
1938:
1928:
1885:
1881:
1870:
1853:
1812:
1808:
1801:
1776:
1772:
1765:
1722:
1718:
1708:
1673:
1670:Neuroscience
1669:
1659:
1629:(1): 101–7.
1626:
1623:Neuroscience
1622:
1616:
1583:
1579:
1572:
1560:. Retrieved
1556:the original
1551:
1542:
1517:
1513:
1506:
1479:
1476:Eur Respir J
1475:
1465:
1433:(2): 136–8.
1430:
1426:
1416:
1391:
1387:
1381:
1348:
1344:
1338:
1295:
1291:
1281:
1256:
1252:
1242:
1217:
1211:
1205:
1180:
1177:Pharmacology
1176:
1166:
1141:
1137:
1130:
1105:
1101:
1091:
1074:
1070:
1064:
1039:
1035:
1029:
1011:
1005:
986:
969:
965:
959:
945:(1): 41–63.
942:
938:
932:
905:
901:
863:
859:
853:
821:(3): 321–8.
818:
814:
774:
770:
732:
728:
722:
705:
701:
695:
678:
674:
668:
643:
639:
633:
611:(2): 311–6.
608:
605:Biochemistry
604:
598:
567:
554:Paraxanthine
552:
540:
526:nitric oxide
522:Dipyridamole
462:
431:
346:
343:Mesembrenone
315:
235:
231:
227:
226:rythro-9-(2-
223:
197:
155:act as both
150:
142:theophylline
126:paraxanthine
96:
72:
39:
37:
3350:Oxytocinase
3158:Transferase
2919:Lisofylline
2914:Furafylline
2873:Theobromine
2838:Doxofylline
2766:Mardepodect
2738:PF-04447943
2733:BAY 73-6691
2647:Mirodenafil
2632:Gisadenafil
2579:Zardaverine
2539:Roflumilast
2519:Piclamilast
2474:Irsogladine
2434:Drotaverine
2419:Crisaborole
2389:Catramilast
2351:Zardaverine
2346:Vesnarinone
2266:Cilostamide
2256:Bucladesine
2198:BAY 60-7550
2180:Vinpocetine
1888:: 476–484.
735:: 441–477.
681:: 195–211.
543:quinazoline
426:antitussive
400:Crisaborole
388:Roflumilast
382:Drotaverine
378:properties.
366:Piclamilast
285:sympathetic
242:BAY 60-7550
194:antagonists
177:leukotriene
167:, activate
151:Methylated
137:theobromine
97:Methylated
61:(cAMP) and
2934:Oxagrelate
2929:Moxaverine
2924:MDL-12330A
2771:Papaverine
2761:Balipodect
2697:Vardenafil
2672:Sildenafil
2622:Dasantafil
2602:Aildenafil
2569:Tofimilast
2564:Tetomilast
2549:Ronomilast
2534:Ro 20-1724
2529:Revamilast
2514:Oglemilast
2504:Mesembrine
2489:Lotamilast
2484:Lirimilast
2479:Lavamilast
2469:Indimilast
2449:Filaminast
2429:Difamilast
2409:Cilomilast
2374:Arofylline
2369:Apremilast
2341:Trequinsin
2336:Siguazodan
2316:Pimobendan
2311:Parogrelil
2296:Meribendan
2271:Cilostazol
2261:Carbazeran
2246:Anagrelide
2203:Carbazeran
2098:2011-08-27
1586:(1): 2–6.
590:References
584:papaverine
569:Papaverine
492:vardenafil
484:Sildenafil
394:Apremilast
310:Pimobendan
300:Cilostazol
295:Anagrelide
210:subtypes.
108:, a minor
86:See also:
3251:Hydrolase
3215:Integrase
3130:Aromatase
3067:Substrate
2976:See also:
2949:Quercetin
2883:Zaprinast
2848:Ibudilast
2781:Tofisopam
2776:TC-E 5005
2715:BRL-50481
2687:Tadalafil
2667:SCH-51866
2642:Lodenafil
2612:Beminafil
2464:ICI-63197
2444:Etazolate
2326:Quazinone
2306:Olprinone
2301:Milrinone
2276:Enoximone
2236:Adibendan
2175:SCH-51866
1961:0955-9930
1902:0028-3908
1829:1521-0111
1077:: 41–63.
488:tadalafil
450:cytokines
410:aporphine
360:Ibudilast
277:enoximone
273:milrinone
230:ydroxy-3-
153:xanthines
110:stimulant
99:xanthines
3428:Category
3297:Protease
2964:Trapidil
2954:Satigrel
2899:Diazepam
2892:Unsorted
2858:Luteolin
2818:Caffeine
2692:Udenafil
2607:Avanafil
2559:RS-25344
2544:Rolipram
2509:Mesopram
2494:Luteolin
2454:Glaucine
2404:CGH-2466
2379:Atizoram
2286:Imazodan
2213:Oxindole
2107:cite web
2089:Archived
2018:19066855
1969:23034509
1920:23261866
1845:14842240
1837:18621927
1793:22100138
1757:19847264
1700:17081698
1651:19578277
1643:15489033
1534:19853596
1498:18094015
1457:21120194
1408:18181659
1373:23923058
1365:17668454
1322:17514358
1313:11138448
1273:10869699
994:Archived
924:15634873
845:18568240
793:11692087
580:striatum
576:alkaloid
558:caffeine
500:avanafil
496:udenafil
446:rhinitis
436:such as
406:Glaucine
372:Luteolin
354:Rolipram
269:Amrinone
248:Oxindole
106:caffeine
3323:Trypsin
2797:BC11-38
2652:MY-5445
2627:Icariin
2554:RPL-554
2459:HT-0712
2399:CDP-840
2394:CC-1088
2331:RPL-554
2066:4325052
2009:2748940
1911:3562388
1748:2783639
1727:Bibcode
1691:3313447
1608:7795640
1600:3063534
1448:2983030
1330:9866539
1234:7680859
1197:1658821
1158:2724296
1122:2456442
1083:3588607
1056:3806581
951:3588607
880:9927365
836:2664230
660:4342220
625:4321663
530:statins
238:denine)
69:History
3377:(EC 4)
3253:(EC 3)
3160:(EC 2)
3120:1.13
3077:(EC 1)
2682:T-0156
2574:YM-976
2291:KMUP-1
2064:
2016:
2006:
1967:
1959:
1918:
1908:
1900:
1843:
1835:
1827:
1791:
1755:
1745:
1719:Nature
1698:
1688:
1649:
1641:
1606:
1598:
1532:
1496:
1455:
1445:
1406:
1371:
1363:
1328:
1320:
1310:
1271:
1232:
1195:
1156:
1120:
1081:
1054:
1022:
949:
922:
878:
843:
833:
791:
747:
714:183099
712:
687:165666
685:
658:
623:
444:, and
438:asthma
422:5-HT2A
48:enzyme
3375:Lyase
3335:Mixed
3328:Renin
3306:DPP-4
3141:1.17
3135:COX-2
3128:1.14
3031:Class
2909:DPCPX
2791:PDE11
2753:PDE10
2092:(PDF)
2085:(PDF)
1862:(PDF)
1841:S2CID
1647:S2CID
1604:S2CID
1562:1 May
1369:S2CID
1326:S2CID
749:17360
573:opium
571:, an
408:, an
376:IGF-1
234:onyl)
76:Weiss
42:is a
3391:4.2
3383:4.1
3358:3.5
3295:3.4
3277:3.2
3259:3.1
3208:2.7
3200:2.6
3187:2.5
3181:PARP
3179:2.4
3168:COMT
3166:2.1
3112:1.5
3104:1.4
3096:1.3
3083:1.1
2853:IBMX
2725:PDE9
2707:PDE7
2589:PDE5
2361:PDE4
2228:PDE3
2208:EHNA
2190:PDE2
2170:MMPX
2162:PDE1
2113:link
2062:PMID
2014:PMID
1965:PMID
1957:ISSN
1916:PMID
1898:ISSN
1833:PMID
1825:ISSN
1789:PMID
1753:PMID
1696:PMID
1639:PMID
1596:PMID
1564:2018
1530:PMID
1494:PMID
1453:PMID
1404:PMID
1361:PMID
1318:PMID
1269:PMID
1230:PMID
1193:PMID
1154:PMID
1118:PMID
1079:PMID
1052:PMID
947:PMID
920:PMID
876:PMID
841:PMID
789:PMID
745:PMID
710:PMID
683:PMID
656:PMID
621:PMID
504:PDE5
498:and
442:COPD
420:and
317:PDE3
275:and
220:EHNA
183:and
175:and
165:cAMP
144:, a
120:IBMX
44:drug
27:Drug
3311:ACE
2828:CPX
2218:PDP
2054:doi
2004:PMC
1996:doi
1992:203
1947:doi
1906:PMC
1890:doi
1886:67C
1817:doi
1781:doi
1743:PMC
1735:doi
1723:461
1686:PMC
1678:doi
1674:144
1631:doi
1627:129
1588:doi
1584:238
1522:doi
1518:627
1484:doi
1443:PMC
1435:doi
1396:doi
1392:108
1353:doi
1308:PMC
1300:doi
1261:doi
1222:doi
1185:doi
1146:doi
1110:doi
1075:230
1044:doi
974:doi
943:230
910:doi
906:174
868:doi
864:159
831:PMC
823:doi
779:doi
775:108
737:doi
648:doi
644:284
613:doi
528:or
206:or
187:and
169:PKA
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