Deprenyl
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| Other names | (+/-)-Deprenyl; (±)-Deprenyl; dl-Deprenyl; (±)-Selegiline; (rac)-Selegiline; E-250; N-Propargylmethamphetamine; N,α-Dimethyl-N-2-propynylphenethylamine; N-Propargyl-N-methylamphetamine; Phenylisopropylmethylpropinylamine |
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| Formula | C13H17N |
| Molar mass | 187.286 g·mol−1 |
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Deprenyl, also known by its developmental code name E-250 and as N-propargylmethamphetamine, is the racemic mixture of D-deprenyl and L-deprenyl (selegiline).[1][2][3] It was discovered in 1961 in Hungary at Chinoin Pharmaceutical Company by Zoltan Ecseri and József Knoll, was patented in 1962, and was first described in the literature in 1964 or 1965.[1][2][3]
The drug is a monoamine oxidase inhibitor and norepinephrine–dopamine releasing agent.[2] It is a prodrug of methamphetamine and amphetamine, which mediates the latter action.[4] Deprenyl was studied clinically at high doses of 50 to 100 mg/day and was described as a psychostimulant and antidepressant.[2][1][3] At lower doses, selective MAO-B inhibition would be expected, but at these higher doses, dual inhibition of MAO-A and MAO-B would occur, on the basis of L-deprenyl.[5]
Subsequent to its synthesis, the stereoisomers of deprenyl were separated.[1] The dextrorotatory isomer, D-deprenyl, was found to be more toxic, producing effects like hyperthermia and more potent psychostimulation in rodents.[1][2] The levorotatory isomer, selegiline, was much more potent as an MAO-B inhibitor, and was subsequently developed for the treatment of Parkinson's disease and depression.[2][3]
Deprenyl is reported to result in side effects including agitation, anxiety, and sleep disturbances more often than selegiline.[6]
Similarly to selegiline, deprenyl is a catecholaminergic activity enhancer (CAE).[7] Both enantiomers of deprenyl, D-deprenyl and selegiline, are active in this respect, but selegiline is slightly more potent than D-deprenyl.[7]
See also
References
- ^ a b c d e Parnham, M. J. (1993). "The History of l-Deprenyl". Inhibitors of Monoamine Oxidase B. Milestones in Drug Therapy (in German). Basel: Birkhäuser Basel. pp. 237–251. doi:10.1007/978-3-0348-6348-3_12. ISBN 978-3-0348-6349-0.
- ^ a b c d e f Heinonen EH, Lammintausta R (1991). "A review of the pharmacology of selegiline". Acta Neurol Scand Suppl. 136: 44–59. doi:10.1111/j.1600-0404.1991.tb05020.x. PMID 1686954.
- ^ a b c d 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.
- ^ Tipton KF (November 2018). "90 years of monoamine oxidase: some progress and some confusion". J Neural Transm (Vienna). 125 (11): 1519–1551. doi:10.1007/s00702-018-1881-5. PMID 29637260.
- ^ Mahmood I (August 1997). "Clinical pharmacokinetics and pharmacodynamics of selegiline. An update". Clin Pharmacokinet. 33 (2): 91–102. doi:10.2165/00003088-199733020-00002. PMID 9260033.
- ^ Knoll J (1983). "Deprenyl (selegiline): the history of its development and pharmacological action". Acta Neurol Scand Suppl. 95: 57–80. doi:10.1111/j.1600-0404.1983.tb01517.x. PMID 6428148.
Tringer at al. (1971) (76) concluded that deprenyl has a favourable effect in endogenous depression. It was claimed by these authors that the racemic form elicited agitation, anxiety and sleep disturbances more frequently than the (-) isomer.
- ^ a b Knoll J, Miklya I (1994). "Multiple, small dose administration of (-)deprenyl enhances catecholaminergic activity and diminishes serotoninergic activity in the brain and these effects are unrelated to MAO-B inhibition". Arch Int Pharmacodyn Ther. 328 (1): 1–15. PMID 7893186.