506:
expectation that the simultaneous administration of this analogue with (–)-BPAP will significantly antagonize the enhancer effect of the latter, proving that they act on the same receptor. The low specific activity of 3-F-BPAP was demonstrated in the rat in the shuttle box. The effect of (–)-BPAP was measured in eight different doses from 0.05 to 10 mg/kg. Even the lowest dose significantly antagonized tetrabenazine-induced inhibition of learning. In contrast, 3-F-BPAP was ineffective in five different doses, ranging from 0.25 to 5.0 mg/kg (34, Table 3). The concurrent administration of 1 mg/kg 3-FBPAP with 0.1 mg/kg (–)-BPAP significantly inhibited the enhancer effect of (–)-BPAP but 1 mg/kg 3-FBPAP did not influence the enhancer effect of 1 mg/kg (–)-BPAP (34, Fig. 2). This is clear indication that the compounds bind to the same receptor to which (–)-BPAP has a much higher affinity than 3-F-BPAP. We studied the effect of 1 and 5 mg/kg (–)-deprenyl in different combinations with 1 and 5 mg/kg 3-F-BPAP and found that 3-F-BPAP left the enhancer effect of (–)-deprenyl unchanged (34, Fig. 2). Furthermore, 3-F-BPAP did not influence the enhancer effect of (–)-PPAP, a (–)- deprenyl analogue free of MAO-B inhibitory potency (34, Fig. 4).
550:
latter, proving that they act on the same receptor. The low specific activity of 3-F-BPAP was demonstrated in the rat in the shuttle box. The effect of (−)-BPAP was measured in eight different doses from 0.05 to 10 mg/kg. Even the lowest dose significantly antagonized tetrabenazine-induced inhibition of learning (see Table 3.1). In contrast, 3-F-BPAP was ineffective in five different doses, ranging from 0.25 to 5.0 mg/kg (Table 3 in Knoll et al. 2002a). The concurrent administration of 1 mg/kg 3-F-BPAP with 0.1 mg/kg (−)- BPAP significantly inhibited the enhancer effect of (−)-BPAP, but 1 mg/kg 3-F-BPAP did not influence the enhancer effect of 1 mg/kg (−)-BPAP (Fig. 2 in Knoll et al. 2002a). This is a clear indication that the compounds bind to the same receptor, to which (−)-BPAP has a much higher affinity than 3-F-BPAP. We studied the effect of 1 and 5 mg/kg (−)-deprenyl in different combinations with 1 and 5 mg/kg 3-F-BPAP and found that 3-F-BPAP left the enhancer effect of (−)-deprenyl unchanged (Fig. 3 in Knoll 2002a). Furthermore, 3-F-BPAP did not influence the enhancer effect of (−)-PPAP, the (−)-deprenyl analogue free of MAO-B inhibitory potency (Fig. 4 in Knoll 2002a).
460:
weak enhancer effect antagonized the effect of (–)-BPAP but did not influence the enhancer effect of selegiline (Knoll et al., 2002a). The results suggest the heterogeneity of enhancer receptors. It was proposed in this study that TA receptors function as enhancer receptors (Knoll et al., 2002a). The assumption is supported by the finding of
Borowsky et al. (2001) that the TA receptors for PEA and tryptamine are not identical.
29:
413:
1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)-aminopentane HCl , a newly synthetized analogue of (–)-BPAP with low specific activity, significantly antagonized the enhancer effect of (–)-BPAP but left the effect of (–)-deprenyl and (–)-PPAP unchanged. This was the first proof for a difference in the
549:
1-(2-Benzofuryl)-2-(3,3,3-trifluoropropyl)-aminopentane HCl (3-F-BPAP), a close structural analogue of BPAP with weak enhancer activity, was synthesized with the expectation that the simultaneous administration of this analogue with (−)-BPAP would significantly antagonize the enhancer effect of the
459:
A recent study furnished direct evidence for the first time that the mechanism through which selegiline, the PEA-derived synthetic enhancer substance, and (–)- BPAP, the tryptamine-derived synthetic enhancer substance, exert their enhancer effects are not identical. An analogue of (–)-BPAP with a
505:
Convincing indirect proof for specific enhancer receptors in the dopaminergic system was already furnished by a recent study (34). 1-(2-Benzofuryl)-2-(3,3,3-trifluoropropyl) aminopentane HCl (3-F-BPAP) a close structural analogue of BPAP with weak enhancer activity was synthesized with the
571:
Knoll J, Miklya I, Knoll B, Yasusa T, Shimazu S, Yoneda F (September 2002). "1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl, 3-F-BPAP, antagonizes the enhancer effect of (-)-BPAP in the shuttle box and leaves the effect of (-)-deprenyl unchanged".
774:
1007:
997:
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Shimazu S, Miklya I (May 2004). "Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives".
767:
387:
Gaszner P, Miklya I (January 2006). "Major depression and the synthetic enhancer substances, (-)-deprenyl and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane".
236:
760:
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Knoll J (August 2003). "Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives".
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331:(PPAP). This suggests that different MAEs like BPAP and selegiline may not be identical in their actions and might be acting via different
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298:
72:
54:
992:
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Miklya I (November 2016). "The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015)".
1012:
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1002:
264:
InChI=1S/C16H20F3NO/c1-2-5-13(20-9-8-16(17,18)19)11-14-10-12-6-3-4-7-15(12)21-14/h3-4,6-7,10,13,20H,2,5,8-9,11H2,1H3
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mechanism of action between a PEA-derived enhancer substance and its tryptamine-derived peer (Knoll et al., 2002a).
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Even the first developed synthetic enhancers, DEP and BPAP, are not identical in their molecular mechanism.52,53
910:
328:
332:
347:
971:
898:
362:
704:"Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline"
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903:
881:
525:
Knoll J (2005). "Enhancer
Regulation: A Neurochemical Approach to the Innate and Acquired Drives".
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than BPAP. The effects of MAEs like BPAP and selegiline appear to be mediated by TAAR1
313:
585:
986:
129:
354:, and hence 3-F-BPAP may be acting as a TAAR1 antagonist (or weak partial agonist).
752:
527:
The Brain and Its Self: A Neurochemical
Concept of the Innate and Acquired Drives
833:
650:"Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum"
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3-F-BPAP has a weak MAE effect itself but with much lower
343:
antagonizes the MAE effects of both BPAP and selegiline.
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529:. Berlin/Heidelberg: Springer-Verlag. pp. 25–94.
44:
3-Fluoro-BPAP; 3-Fluoro-Benzofuranylpropylaminopentane
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819:
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361:and colleagues and was first described in the
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702:Harsing LG, Timar J, Miklya I (August 2023).
648:Harsing LG, Knoll J, Miklya I (August 2022).
308:Conversely, 3-F-BPAP does not antagonize the
8:
19:
1008:Monoaminergic activity enhancer antagonists
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148:
27:
16:Monoaminergic activity enhancer antagonist
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435:Prog Neuropsychopharmacol Biol Psychiatry
389:Prog Neuropsychopharmacol Biol Psychiatry
998:Drugs with unknown mechanisms of action
374:
335:. In contrast to 3-F-BPAP however, the
261:
241:
77:
84:-(3,3,3-trifluoropropyl)pentan-2-amine
18:
7:
310:catecholaminergic activity enhancer
244:CCCC(CC1=CC2=CC=CC=C2O1)NCCC(F)(F)F
119:
14:
784:Monoaminergic activity enhancers
188:
182:
176:
968:Monoamine metabolism modulators
299:monoaminergic activity enhancer
269:Key:JCZRCOLYSDAPPW-UHFFFAOYSA-N
55:Monoaminergic activity enhancer
851:Benzofuranylpropylaminopentane
291:benzofuranylpropylaminopentane
191:
170:
1:
964:Monoamine reuptake inhibitors
956:Receptor/signaling modulators
586:10.1016/s0024-3205(02)01968-9
447:10.1016/j.pnpbp.2003.11.016
401:10.1016/j.pnpbp.2005.06.004
1034:
960:Monoamine releasing agents
357:3-F-BPAP was developed by
160:Chemical and physical data
1018:Trifluoromethyl compounds
948:
888:Indolylpropylaminopentane
252:
232:
68:
26:
911:Phenylpropylaminopentane
329:phenylpropylaminopentane
535:10.1007/3-540-27434-0_4
493:10.1023/a:1024224311289
80:1-(1-benzofuran-2-yl)-
993:Benzofuranethanamines
899:Dextromethamphetamine
721:10.3390/ijms241713334
363:scientific literature
312:(CAE) effects of the
301:(MAE) effects of the
1013:Receptor antagonists
667:10.3390/ijms23158543
904:Levomethamphetamine
882:Desmethylselegiline
621:10.1038/mp.2016.127
23:
1003:Experimental drugs
980:
979:
975:
875:
864:
839:Dextroamphetamine
615:(11): 1499–1503.
580:(17): 1975–1984.
544:978-3-540-23969-7
333:receptor subtypes
326:
293:(BPAP) and is an
277:
276:
223:Interactive image
107:501901-69-5 (HCl)
1025:
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873:
862:
829:4-Fluorodeprenyl
800:Phenylethylamine
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487:(8): 1275–1297.
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327:-deprenyl) and
305:-related BPAP.
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36:Clinical data
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922:Antagonists
834:Amphetamine
395:(1): 5–14.
339:antagonist
284:fluorinated
206: g·mol
103:501901-68-4
64:Identifiers
41:Other names
987:Categories
940:Rasagiline
876:-deprenyl)
870:Selegiline
806:Tryptamine
792:Endogenous
369:References
321:selegiline
303:tryptamine
295:antagonist
287:derivative
211:3D model (
199:Molar mass
141:ChemSpider
94:CAS Number
73:IUPAC name
58:antagonist
50:Drug class
953:See also:
865:-Deprenyl
821:Synthetic
365:in 2002.
282:is the 3-
930:3-F-BPAP
857:Deprenyl
811:Tyramine
740:37686140
731:10487936
686:35955676
629:27480491
594:12175892
574:Life Sci
501:12834268
455:15093948
409:16023777
280:3-F-BPAP
130:10125543
21:3-F-BPAP
677:9369307
352:agonism
348:potency
318:derived
297:of the
204:299.337
166:Formula
150:8301062
116:PubChem
913:(PPAP)
890:(IPAP)
853:(BPAP)
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728:
684:
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627:
592:
541:
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237:SMILES
935:EPPTB
884:(DMS)
802:(PEA)
341:EPPTB
337:TAAR1
257:InChI
213:JSmol
736:PMID
682:PMID
625:PMID
590:PMID
539:ISBN
497:PMID
451:PMID
405:PMID
726:PMC
716:doi
672:PMC
662:doi
617:doi
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489:doi
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289:of
120:CID
989::
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325:L
323:(
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192:O
189:N
186:3
183:F
177:H
171:C
82:N
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