Elsevier

Biochemical Pharmacology

Volume 28, Issue 7, 1 April 1979, Pages 995-1002
Biochemical Pharmacology

Cumulative effects of irreversible MAO inhibitors in vivo

https://doi.org/10.1016/0006-2952(79)90293-4Get rights and content

Abstract

The effects of repeated treatment with clorgyline, pargyline, deprenyl and tranylcypromine on MAO activity in rat brain and liver were investigated. MAO was measured with the substrates serotonin (5HT), phenethylamine (PEA) and, in some cases, t brain tissue after single and repeated administrations of 10 mg/kg s.c. clorgyline or deprenyl were also compared. Single doses of clorgyline (1 and 10 mg/kg s.c.) completely blocked the deamination of 5-HT. PEA deamination gradually decreased during the 14-day treatment. Pargyline in a dose of 0.3 mg/kg s.c. reduced both 5-HT and PEA deamination progressively over the same period. In the course of repeated treatment the effects of clorgyline and deprenyl on 5-HT and PEA deamination increased in intensity, by a factor of about 10 in the brain and about 3 in the liver. The potentiation of the effect of tranylcypromine was less marked (brain: × 4; liver: × 2). The rates of recovery of MAO activity were not greater after repeated than after single administrations of high doses of clorgyline and deprenyl, suggesting that the withdrawal of the drugs is not followed by a rebound phenomenon. Our results indicate that repeated treatment with suitable doses of clorgyline or deprenyl leads to specific reduction of either MAO A or B activity in brain, without producing any appreciable effect in the liver.

References (16)

  • N.H. Neff et al.

    Life Sci.

    (1974)
  • C.J. Fowler et al.

    Biochem. Pharmac.

    (1978)
  • J.P. Johnston

    Biochem. Pharmac.

    (1968)
  • R.F. Long et al.

    Biochem. Pharmac.

    (1976)
  • P.C. Waldmeier et al.

    Biochem. Pharmac.

    (1978)
  • R.J. Wurtman et al.

    Biochem. Pharmac.

    (1963)
  • K.F. Tipton et al.

    Nature, New Biol.

    (1973)
  • M.D. Houslay

    J. Pharm. Pharmac.

    (1977)
There are more references available in the full text version of this article.

Cited by (81)

  • Selegiline induces a wake promoting effect in rats which is related to formation of its active metabolites

    2016, Pharmacology Biochemistry and Behavior
    Citation Excerpt :

    Although selegiline is rapidly cleared from the system, the covalent binding of selegiline to MAO results in reduced enzyme recovery and interferes with enzyme synthesis after prolonged treatment (Youdim, 1978). It was found that the rat brain activity of MAO-B was abolished after treatment with 10 mg/kg selegiline requiring 8 days to return to 50% of its normal activity following a single dose (Felner and Waldmeier, 1979). Accordingly, it can be assumed the final day of the dose escalation, no functional MAO-B remained in the brain, thereby further implicating the psychoactive metabolites in the wake promoting effects seen.

  • Monoamine oxidase A and B inhibiting effect and molecular modeling of some synthesized coumarin derivatives

    2013, Neurochemistry International
    Citation Excerpt :

    These drawbacks were thought to be related to nonselective and irreversible enzyme inhibition. In addition, subchronic administration of irreversible MAOIs caused very marked increase in brain 5-HT (prolonged sympathomimetic and serotonin toxicity) accompanied by profound decrease in 5-HIAA levels that is likely due to the cumulative effect produced by irreversible MAOIs (Wimbiscus et al., 2010 and Felner and Waldmaier, 1979). In recent years, efforts have been focused on the discovery of reversible and selective MAOIs and this has led to a new class of compounds.

  • Selegiline transdermal system: Current awareness and promise

    2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry
View all citing articles on Scopus
View full text