Cumulative effects of irreversible MAO inhibitors in vivo
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Selegiline induces a wake promoting effect in rats which is related to formation of its active metabolites
2016, Pharmacology Biochemistry and BehaviorCitation 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.
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2013, Neurochemistry InternationalCitation 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.
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