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| Routes of administration | Oral |
| Drug class | Dopamine reuptake inhibitor |
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| ECHA InfoCard | 100.046.581 |
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| Formula | C12H17N |
| Molar mass | 175.275 g·mol−1 |
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2-Benzylpiperidine is astimulantdrug of thearylpiperidine family. It is similar instructure to certain other stimulants such asmethylphenidate anddesoxypipradrol. However, it is far lesspotent as amonoamine reuptake inhibitor in comparison.[1][2][3] The drug is little used as a stimulant, with its main use being as asynthetic intermediate in themanufacture of other drugs.[4][5][6]
Theaffinity (Ki) of 2-benzylpiperidine for thedopamine transporter (DAT) has been reported to be 6,360 nM and itsfunctional inhibition (IC50) of the DAT has been reported to be 3,780 to 8,800 nM.[1][2][3] These values were 85-fold and 53- to 38-fold lower than those of methylphenidate, respectively.[1][2][3] It produced 36% inhibition of binding to thenorepinephrine transporter (NET) and 22% inhibition of binding to theserotonin transporter (SERT) at a concentration of 10,000 nM.[3] However,2-phenylpiperidine might have actually been assayed by mistake in one of the two studies that reported the preceding values, and so some of the values might be incorrect.[1] In another older study, 2-benzylpiperidine was reported to be similarly potent todextroamphetamine in terms ofnorepinephrine reuptake inhibition.[7]
Derivatives of 2-benzylpiperidine, such as thecathinone-like derivativeα-keto-2-benzylpiperidine and its 4-methyl, 4-halo, and 3,4-dichloro analogues, have been synthesized and have been found to be much more potent asdopamine reuptake inhibitors.[1] Another analogue of 2-benzylpiperidine,3-phenylpiperidine, is also more potent as a monoamine reuptake inhibitor in comparison, with higher affinities for themonoamine transporters and ~8-fold higher functional inhibition of the DAT.[3]
Compound 5 [(2-benzylpiperidine)] has also, apparently, been previously prepared and examined as a DAT reuptake inhibitor by Kim et al.6 However, there is a potential problem. Although Kim et al.6 showed the correct chemical structure for 2-benzylpiperidine, their experimental writeup suggests they might have inadvertently prepared 2-phenylpiperidine. Furthermore, their melting point for the target is different from that previously reported by others for the target compound.23,24 Obviously, apart from the different melting point, this might have been a typographical error.
8 Complete removal of the ester of tMP (i.e., 2-benzylpiperidine, 130) reduced the binding affinity at DAT by 85-fold (IC50 = 6360 nM) and reduced [ 3H]DA reuptake potency by 38-fold (IC50 = 8800 nM) as compared to tMP (70) (IC50 =75 and 230 nM, binding affinity and [ 3H]DA uptake, respectively).125 [...] We also showed that the carbonyl oxygen atom of 161 is not important for the compound to act as a DAT reuptake inhibitor as our descarbonyl analog (2-benzylpiperidine, 169) retained activity; however, the carbonyl oxygen atom helps to improve the potency at DAT as a reuptake inhibitor.
[...] removal of the additional phenyl ring of deoxypipradrol or the carbomethoxy group of methylphenidate yields 2-benzylpiperidine which contains the intact piperidine ring and is as potent as S-(+)-amphetamine as an inhibitor of norepinephrine uptake into synaptic vesicles (unpublished observations). [...]
