Summary
The monoamine oxidase (MAO) B activity of rat brain was inhibited by selegiline and its desmethyl-metabolite in vitro with IC50-values of 11.25 nmol/1 and 625.00 nmol/1, respectively. When measured in an ex vivo experiment following oral treatment of rats, the large difference in potency was distinctly reduced, from factor 60 in vitro to factor 3 ex vivo. Restoration experiments of MAO-B-activity after cessation of treatment revealed a nearly identical time course for both compounds. It is concluded that desmethyl-selegiline is an irreversible blocker of MAO-B, nearly equipotent to selegiline after multiple oral administration. No pharmacologically relevant inhibition of MAO-A was found with both compounds.
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References
Barbeau A, Murphy CF, Sourkes TL (1961) Excretion of dopamine in diseases of basal ganglia. Science 133:1706.
Birkmayer W, Hornijkiewicz O (1961) Der L-3,4 Dioxyphenylalanin (L-Dopa)-Effekt bei der Parkinson-Akinesie. Wien Klin Wochenschr 73:787.
Birkmayer W, Riederer P, Ambrozi L, Youdim MBH (1977) Implications of combined treatment with ‘Madopar’ and L-deprenyl in Parkinson’s disease. Lancet i:439–443.
Finberg JPM, Youdim MBH (1983) Selective MAO-A and MAO-B inhibitors: their mechanism of action and pharmacology. Neuropharmacology 22:441–446.
Glover V, Sandier M, Owen F, Riley GJ (1977) Dopamine is a monoamine oxidase B substrate in man. Nature 265:80–81.
Knoll J (1976) Analysis of the pharmacological effects of selective monoamine oxidase inhibitors. In: Wolstenholme GEW, Knight J (eds) Monoamine oxidase and its inhibition. Elsevier, Amsterdam, pp 135–161.
Maycock AL, Abeles RH, Salach JI, Singer TP (1976) The action of acetylenic inhibitors on mitochondrial monoamine oxidase: structure of the flavin site in the inhibited enzyme. In: Wolstenholme GEW, Knight J (eds) Monoamine oxidase and its inhibition. Elsevier, Amsterdam, pp 33–47.
Mutschier E, Möhrke W (1983) Kinetics of MAO inhibitors. Mod Probl Pharmacopsychiatry 19:126–134.
Salach JI, Detmer K, Youdim MBH (1979) The reaction of bovine and rat liver monoamine oxidase with 14C-clorgyline and 14C-deprenyl. Mol Pharmacol 16:234–241.
Yoshida T, Yamada Y, Yamamoto T, Kuroiwa Y (1986) Metabolism of deprenyl a selective monoamine oxidase (MAO) B inhibitor in rat: relationship to MAO-B inhibitory potency. Xenobiotica 16(2): 129–136.
Young WF, Laws ER, Sharbrough FW, Weinshilboum RM (1986) Human monoamine oxidase. Arch Gen Psychiatry 43:604–609.
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© 1990 Springer-Verlag
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Borbe, H.O., Niebch, G., Nickel, B. (1990). Kinetic evaluation of MAO-B-activity following oral administration of selegiline and desmethyl-selegiline in the rat. In: Riederer, P., Youdim, M.B.H. (eds) Amine Oxidases and Their Impact on Neurobiology. Journal of Neural Transmission, vol 32. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9113-2_18
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DOI: https://doi.org/10.1007/978-3-7091-9113-2_18
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-82239-5
Online ISBN: 978-3-7091-9113-2
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