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| Other names | Trifluoro-BPAP; Trifluoro-benzofuranylpropylaminopentane |
| Drug class | Monoaminergic activity enhancerantagonist |
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| Chemical and physical data | |
| Formula | C16H20F3NO |
| Molar mass | 299.337 g·mol−1 |
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3-F-BPAP is a trifluorinatedderivative ofbenzofuranylpropylaminopentane (BPAP) and is anantagonist of themonoaminergic activity enhancer (MAE) effects of thetryptamine-related BPAP.[1][2][3][4][5]
Conversely, 3-F-BPAP does not antagonize thecatecholaminergic activity enhancer (CAE) effects of thephenethylamine-derivedselegiline (L-deprenyl) andphenylpropylaminopentane (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 differentreceptor subtypes.[1][2][3][4][6][5] In contrast to 3-F-BPAP however, theTAAR1 antagonistEPPTB antagonizes the MAE effects of both BPAP and selegiline.[7][8]
3-F-BPAP has a weak MAE effect itself but with much lowerpotency than BPAP.[2][3][4][5] The effects of MAEs like BPAP and selegiline appear to be mediated by TAAR1agonism, and hence 3-F-BPAP may be acting as a TAAR1 antagonist (or weakpartial agonist).[7][8][5]
3-F-BPAP was developed byJózsef Knoll and colleagues and was first described in thescientific literature in 2002.[5]
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).
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.
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).
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).
Even the first developed synthetic enhancers, DEP and BPAP, are not identical in their molecular mechanism.52,53