3-F-BPAP

3-F-BPAP

Clinical data
Other names	Trifluoro-BPAP; Trifluoro-benzofuranylpropylaminopentane
Drug class	Monoaminergic activity enhancer antagonist
Identifiers
IUPAC name 1-(1-benzofuran-2-yl)-N-(3,3,3-trifluoropropyl)pentan-2-amine
CAS Number	501901-68-4 501901-69-5 (HCl)
PubChem CID	10125543
ChemSpider	8301062
Chemical and physical data
Formula	C16H20F3NO
Molar mass	299.337 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CCCC(CC1=CC2=CC=CC=C2O1)NCCC(F)(F)F
InChI 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 Key:JCZRCOLYSDAPPW-UHFFFAOYSA-N

3-F-BPAP is a trifluorinated derivative of benzofuranylpropylaminopentane (BPAP) and is an antagonist of the monoaminergic activity enhancer (MAE) effects of the tryptamine-related BPAP.^{[1][2][3][4][5]}

Conversely, 3-F-BPAP does not antagonize the catecholaminergic activity enhancer (CAE) effects of the phenethylamine-derived selegiline (L-deprenyl) and phenylpropylaminopentane (PPAP).^[1][2][3][4] This suggests that different MAEs like BPAP and selegiline may not be identical in their actions and might be acting via different receptor subtypes.^{[1][2][3][4][6][5]} In contrast to 3-F-BPAP however, the TAAR1 antagonist EPPTB antagonizes the MAE effects of both BPAP and selegiline.^[7][8]

3-F-BPAP has a weak MAE effect itself but with much lower potency than BPAP.^[2][3][4][5] The effects of MAEs like BPAP and selegiline appear to be mediated by TAAR1 agonism, and hence 3-F-BPAP may be acting as a TAAR1 antagonist (or weak partial agonist).^[7][8][5]

3-F-BPAP was developed by József Knoll and colleagues and was first described in the scientific literature in 2002.^[5]

References

1. Gaszner P, Miklya I (January 2006). "Major depression and the synthetic enhancer substances, (-)-deprenyl and R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane". Prog Neuropsychopharmacol Biol Psychiatry. 30 (1): 5–14. doi:10.1016/j.pnpbp.2005.06.004. PMID 16023777. 1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)-aminopentane HCl [3-F-BPAP], 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 mechanism of action between a PEA-derived enhancer substance and its tryptamine-derived peer (Knoll et al., 2002a).
2. Shimazu S, Miklya I (May 2004). "Pharmacological studies with endogenous enhancer substances: beta-phenylethylamine, tryptamine, and their synthetic derivatives". Prog Neuropsychopharmacol Biol Psychiatry. 28 (3): 421–427. doi:10.1016/j.pnpbp.2003.11.016. PMID 15093948. 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 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.
3. Knoll J (August 2003). "Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives". Neurochem Res. 28 (8): 1275–1297. doi:10.1023/a:1024224311289. PMID 12834268. 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 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).
4. Knoll J (2005). "Enhancer Regulation: A Neurochemical Approach to the Innate and Acquired Drives". The Brain and Its Self: A Neurochemical Concept of the Innate and Acquired Drives. Berlin/Heidelberg: Springer-Verlag. pp. 25–94. doi:10.1007/3-540-27434-0_4. ISBN 978-3-540-23969-7. 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 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).
5. 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". Life Sci. 71 (17): 1975–1984. doi:10.1016/s0024-3205(02)01968-9. PMID 12175892.
6. Miklya I (November 2016). "The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015)". Mol Psychiatry. 21 (11): 1499–1503. doi:10.1038/mp.2016.127. PMID 27480491. Even the first developed synthetic enhancers, DEP and BPAP, are not identical in their molecular mechanism.52,53
7. Harsing LG, Knoll J, Miklya I (August 2022). "Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum". Int J Mol Sci. 23 (15): 8543. doi:10.3390/ijms23158543. PMC 9369307. PMID 35955676.
8. Harsing LG, Timar J, Miklya I (August 2023). "Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline". Int J Mol Sci. 24 (17): 13334. doi:10.3390/ijms241713334. PMC 10487936. PMID 37686140.