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Efficacy of Pirlindole, a Highly Selective Reversible Inhibitor of Monoamine Oxidase Type A, in the Prevention of Experimentally Induced Epileptic Seizures

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Summary

Intraperitoneal administration of pirlindole (pirazidole) or ‘soluble pirlindole’ 50 mg/kg body-weight prolonged the onset of seizures and decreased the intensity of seizures in rats genetically selected for high sensitivity to audiogenic hereditary epilepsy [Krushinsky-Molodkina (KM) rats]. In this experimental model of epilepsy, pirlindole prevented qualitative alteration (transformation) in the catalytic activity of membrane-bound type A monoamine oxidases (MAO-A), pathogenetically important for the development of the audiogenic seizures. Modification of the enzymatic properties of the monoamine oxidases causes an increase in γ-aminobutyric acid (GABA) deamination in the mitochondrial fraction of the brain. The data obtained suggest that selective inhibitors of MAO-A, such as pirlindole, may prevent experimental epileptic seizures.

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Authors and Affiliations

  1. Institute of Biological and Medical Chemistry, Academy of Medical Sciences, Pogodinskaya 10, Moscow, 119832 GSP, Russia

    A. Medvedev & V. Gorkin

  2. Centre of Drug Chemistry - the All-Union Institute of Pharmaceutical Chemistry, Moscow, Russia

    V. Shvedov & O. Fedotova

  3. Biological Faculty, MV Lomonosov State University, Moscow, Russia

    I. Fedotova & A. Semiokhina

Authors
  1. A. Medvedev
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  2. V. Gorkin
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  3. V. Shvedov
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  4. O. Fedotova
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  5. I. Fedotova
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  6. A. Semiokhina
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Medvedev, A., Gorkin, V., Shvedov, V. et al. Efficacy of Pirlindole, a Highly Selective Reversible Inhibitor of Monoamine Oxidase Type A, in the Prevention of Experimentally Induced Epileptic Seizures. Drug Invest 4, 501–507 (1992). https://doi.org/10.1007/BF03259215

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