Summary
A number of new deprenyl analogues were synthesized during the last decades and structure-activity relationship studies were carried out with the compounds. Among these derivatives U-1424 [N-methyl-N-pro-pargyl-(2-furyl-l-methyl)-ethyl ammonium] and J-508 [N-methyl-N-pro-pargyl-(l-indanyl) ammonium] preserved the selectivity to MAO-B, but the former is slightly less potent inhibitor of the enzyme, while J-508 is more effective than the parent compound. The studies led us to the conclusion that, in the case of a selective and irreversible inhibitor, it is not a proper aim to search for a more potent inhibitor than deprenyl. Nevertheless, the effects of the new derivatives independent of the enzyme inhibitory potency can be beneficial. In this respect p-fluoro-deprenyl (PFD) seems to be promising.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Brodie BB, Cho AK, Gessa GL (1970) Possible role of p-hydroxynorephedrine in the depletion of norepinephrine induced by d-amphetamine and in tolerance to this drug. In: Costa E, Garatini S (ed) Amphetamines and related compounds. Raven Press, New York, pp 217–230.
Ekstedt B, Magyar K, Knoll J (1978) Does the B form selective monoamine oxidase inhibitor lose selectivity by long term treatment?. Biochem Pharmacol 28: 919–923.
Finnegan KT, Skratt JJ, Irwin I, DeLanney LE, Langston JW (1990) Protection against DSP-4-induced neurotoxicity by deprenyl is not related to its inhibition of MAO-B. Eur J Pharmacol 184: 119–126.
Goldstein M, Anagnoste B (1965) The conversion in vivo of d-amphetamine to (+)-p-hydroxy-norephedrine. Biochim Biophys Acta 107: 166–168.
Heinonen EH, Myllyla, V, Sotaniemi K, Lammintausta R, Salonen JS, Anttila M, Savijärvi M, Kotila M, Rinne UK (1989) Pharmacokinetics and metabolism of selegiline. Acta Neurol Scand 126: 93–99.
Knoll J (1983) (-)-Deprenyl (selegiline): the history of its development and pharmacological action. Acta Neurol Scand [Suppl] 95: 57–80.
Knoll J, Magyar K (1972) Some puzzling pharmacological effects of monoamine oxidase inhibitors. In: Costa E, Sandier M (eds) Monoamine oxidases. New vistas. Raven Press, New York, pp 393–408 (Adv Biochem Psychopharmacol, vol 5).
Knoll J, Ecseri Z, Kelemen K, Nievel J, Knoll B (1965) Phenylisopropylmethylpro-pinylamine (E-250), and new spectrum psychic energizer. Arch Int Pharmacodyn Ther 155: 154–164.
Knoll J, Ecseri Z, Magyar K, Sátory é (1978) Novel (-)-deprenyl — derived selective inhibitors of B-type monoamine oxidase. The relation of structure to their action. Biochem Pharmacol 27: 1739–1747.
Langston JW (1980) Selegiline as neuroprotectiv therapy in Parkinson’s disease: concepts and controversies. Neurology 40[Suppl 3]: 61–66.
Magyar K (1991) Neuroprotective effect of deprenyl and p-fluor-deprenyl. In: Fazekas F, Schmutzharol E, Zeiler K (eds) Paneuropean Society of Neurology, Second Congress, Vienna, p 26 (Abstract).
Magyar K, Szüts T (1982) The fate of (-)-deprenyl in the body. Preclinical studies. In: Proceedings of the International Symposium on (-)-deprenyl, Jumex, Szombathely, Hungary, 1982. Chinoin, Budapest, pp 25-31.
Magyar K, Ecseri Z, Bernáth G, Sátory É, Knoll J (1980) Structure-activity relationship of selective inhibitors of MAO-B. In: Magyar K (ed) Monoamine oxidases and their selective inhibition. Pergamon Press, Budapest, pp 11–21.
Magyar K, Tóthfalusi L (1984) Pharmacokinetic aspects of deprenyl effects. Pol J Pharmacol Pharm 36: 373–384.
Magyar K, Vizi ES, Ecseri Z, Knoll J (1967) Comparative pharmacological analysis of the optical isomers of phenyl-isopropyl-methyl-propinylamine (E-250). Acta Physiol Hung 32: 377–387.
Magyar K, Skolnik J, Knoll J (1968) Radiopharmacological analytic studies with deprenyl-14C. In: Leszkowszky GP (ed) V. Conferencia Hungarica pro Therapia et Investigatione in Pharmacologia. Budapest Publ House. Acad Sci, Budapest, pp 103–109.
Reynolds GP, Elsworth JD, Blau K, Sandier M, Lees AJ, Stern GM (1978) Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol 6: 542–554.
Ross SB (1976) Long-term effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurons in the rat brain and heart. Br J Pharmacol 58: 521–527.
Snyder SH, Coyle JT (1969) Regional differences in 3H-norepinephrine and 3H-dopamine uptake into rat brain homogenates. J Pharmacol Exp Ther 165: 78–86.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer-Verlag
About this paper
Cite this paper
Magyar, K. (1994). Behaviour of (-)-deprenyl and its analogues. In: Tipton, K.F., Youdim, M.B.H., Barwell, C.J., Callingham, B.A., Lyles, G.A. (eds) Amine Oxidases: Function and Dysfunction. Journal of Neural Transmission, vol 41. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9324-2_23
Download citation
DOI: https://doi.org/10.1007/978-3-7091-9324-2_23
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-82521-1
Online ISBN: 978-3-7091-9324-2
eBook Packages: Springer Book Archive