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Related Experiment Videos

Calcium channel blockade: possible explanation for thioridazine's peripheral side effects.

R J Gould, K M Murphy, I J Reynolds

    The American Journal of Psychiatry
    |March 1, 1984
    PubMed
    Summary

    Thioridazine exhibits calcium channel antagonist activity, potentially explaining its cardiac and sexual side effects. This effect was observed at therapeutic blood levels, suggesting a direct pharmacological mechanism.

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    [3H](+)MK801 radioligand binding assay at the N-methyl-D-aspartate receptor.

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    Area of Science:

    • Pharmacology
    • Cardiovascular Science
    • Neuroscience

    Background:

    • Thioridazine is an antipsychotic medication with known cardiac and sexual side effects.
    • The underlying mechanisms for these side effects are not fully understood.

    Purpose of the Study:

    • To investigate whether thioridazine possesses calcium channel antagonist activity.
    • To determine if this activity correlates with observed clinical side effects.

    Main Methods:

    • Utilized radioligand binding assays with 3H-nitrendipine to assess thioridazine's interaction with voltage-operated calcium channels.
    • Performed functional assays using isolated rat vas deferens to measure thioridazine's effect on calcium-dependent contractions.

    Main Results:

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    • Thioridazine demonstrated inhibitory effects on 3H-nitrendipine binding to calcium channels, similar to verapamil.
    • Thioridazine exhibited comparable potency in antagonizing potassium-induced, calcium-dependent contractions of rat vas deferens.
    • The concentrations of thioridazine showing calcium channel antagonist effects were consistent with therapeutic blood levels.

    Conclusions:

    • Thioridazine possesses significant calcium channel antagonist activity.
    • This calcium antagonist property likely contributes to the cardiac and sexual side effects associated with thioridazine use.
    • The findings provide a pharmacological basis for understanding thioridazine's adverse effects.