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Related Experiment Videos

Tyramine pressor sensitivity changes during deprenyl treatment.

T Sunderland, E A Mueller, R M Cohen

    Psychopharmacology
    |January 1, 1985
    PubMed
    Summary

    Deprenyl, a monoamine oxidase (MAO) inhibitor, shows dose-dependent effects in patients with depression. Higher deprenyl doses increase tyramine sensitivity, indicating reduced MAO-A inhibition and potential side effects.

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    Area of Science:

    • Pharmacology
    • Neuroscience
    • Psychiatry

    Background:

    • Deprenyl is recognized as a selective monoamine oxidase (MAO) type B inhibitor.
    • Selective MAO-B inhibition is typically associated with minimal enhancement of tyramine's pressor effects.

    Purpose of the Study:

    • To investigate the effects of varying deprenyl doses on tyramine pressor response in depressed patients.
    • To compare deprenyl's effects with a mixed MAO inhibitor, tranylcypromine.

    Main Methods:

    • Utilized an intravenous steady-state tyramine infusion technique.
    • Administered different doses of deprenyl (10, 30, 60 mg/day) and tranylcypromine to 11 depressed patients over 3 weeks.
    • Measured changes in tyramine sensitivity and plasma 3-methoxy,4-hydroxyphenylglycol (MHPG) levels.

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    Main Results:

    • Deprenyl demonstrated dose-proportionate increases in tyramine sensitivity across all tested doses (10-60 mg/day).
    • The 60 mg/day deprenyl dose resulted in a significant (22-fold) increase in tyramine sensitivity, comparable to tranylcypromine.
    • Reductions in plasma MHPG, an indicator of MAO-A inhibition, strongly correlated with increased tyramine pressor sensitivity (r = 0.82).

    Conclusions:

    • Deprenyl exhibits dose-dependent selectivity, acting as a MAO-B inhibitor at lower doses.
    • Higher deprenyl doses lead to a loss of selectivity, causing significant MAO-A inhibition ('crossover') and increased tyramine pressor sensitivity.
    • These findings highlight the importance of dosage in deprenyl's pharmacological profile and potential clinical implications.