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Drug Investigation

, Volume 4, Issue 6, pp 501–507 | Cite as

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

  • A. Medvedev
  • V. Gorkin
  • V. Shvedov
  • O. Fedotova
  • I. Fedotova
  • A. Semiokhina
Original Research Article

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.

Keywords

Monoamine Oxidase Drug Invest Amine Oxidase Clorgyline Audiogenic Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Akopyan ZI, Stesina LN, Gorkin VZ. New properties of highly purified bovine liver mitochondrial monoamine oxidase. Reversible oxidation of sulphydryl groups and reversible qualitative alteration (transformation) of substrate and inhibitor specificity. Journal of Biological Chemistry 246: 4610–4618, 1971Google Scholar
  2. Baumanis EA, Birska IA, Reikhman GO, Shvedov VI, Gorkin VZ. On the mechanisms of modification by pirazidole of the catalytic activity of mitochondrial monoamine oxidase. Voprosy Meditsinskoi Khimii 6: 90–96, 1987Google Scholar
  3. Dvoryantseva GG, Polshakov VI, Sheinker YN, Shvedov VI, Grinev AN, et al. Structure-activity relationships in pyrazino [3,2,1-j,k] carbazole derivatives. A new antidepressant, pirlindole, and related compounds. European Journal of Medicinal Chemistry 20: 414–418, 1985Google Scholar
  4. Gorkin VZ. Monoamine oxidases: versatility of catalytic properties and possible biological functions. Advances in Pharmacology and Chemotherapy 11: 1–50, 1973PubMedCrossRefGoogle Scholar
  5. Gorkin VZ. Monoamine oxidase inhibitors and the transformation of monoamine oxidases. In Wolstenholme GEW & Knight J (Eds) Monoamine oxidase and its inhibitors, pp. 61–81, Elsevier, Amsterdam, 1976Google Scholar
  6. Gorkin VZ. Enzyme transformations. In Quagliariello E, Palmieri E, Singer TP (Eds) Horizons in biochemistry and biophysics, Vol. 3, pp. 1–35, Addison-Wesley Publishing Company, London, 1977Google Scholar
  7. Gorkin VZ. Amine oxidases in clinical research. Pergamon Press, Oxford, New York, 1983Google Scholar
  8. Gorkin VZ. Studies on the nature and specific inhibition of monoamine oxidases. In Kelemen K, Magyar K & Vizi ES (Eds) Neuropharmacology 1985, pp. 9–14, Budapest, 1985aGoogle Scholar
  9. Gorkin VZ. Qualitative alteration (transformation) in catalytic activity of amine oxidases. In Mondovi B (Ed) Structure and functions of amine oxidases, pp. 205–208, CRC Press, Boca Raton, Florida, 1985bGoogle Scholar
  10. Gornall AG, Bardawill CJ, David M. Determination of serum proteins by means of biuret reaction. Journal of Biological Chemistry 177: 751–766, 1949PubMedGoogle Scholar
  11. Goroshinskaya IA, Bronovitskaya ZG, Gorkin VZ. The effect of selective monoamine oxidase inhibitors on rat brain mitochondrial monoamine oxidase during hyperbaric oxygenation. Communications in Psychopharmacology 1: 39–47, 1977PubMedGoogle Scholar
  12. Hajos F. An improved method for the preparation of synaptosomal fraction of high purity. Brain Research 93: 485–489, 1975PubMedCrossRefGoogle Scholar
  13. Kagan VE. Lipid peroxidation in biomembranes. CRC Press, Inc., Boca Raton, Florida, 1988Google Scholar
  14. Kaiser ET, Lawrence DS, Rokita SE. The chemical modification of enzymatic specificity. Annual Review of Biochemistry 54: 565–595, 1985PubMedCrossRefGoogle Scholar
  15. Krushinsky LV. Biological basis of reasoning ability, pp. 114–115, University Press, Moscow, 1986Google Scholar
  16. Kryzhanovsky GN. Pathology of regulatory mechanisms. Patologicheskaia Fiziologiia Eksperimentalnaia Terapiia 2: 3–8, 1990Google Scholar
  17. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. Journal of Biological Chemistry 193: 165–175, 1951Google Scholar
  18. Martorana PA, Heucke U, Nitz RE. The new antidepressant pirlindole. Antagonism of acute overdosage in the mouse. Arzneimittel-Forschung — Drug Research 29: 950–952, 1979Google Scholar
  19. Martorana PA, Nitz RE. The new antidepressant pirlindole. A comparison with Imipramine and tranylcypromine. Arzneimittel-Forschung — Drug Research 29: 946–949, 1979Google Scholar
  20. Mashkovsky M, Andreeva N. Pharmacological properties of 2,3,3a,4,5,6-hexahydro-8-methyl-1h-pyrazino 3,2,1-j,k carbazole hydrochloride (Pirlindole), a new antidepressant. Arzneimittel-Forschung — Drug Research 31: 75–79, 1981Google Scholar
  21. Mashkovsky MD, Andreeva NI, Polezhaeva AI. Pharmacology of antidepressants. Meditsina, Moscow, 1983Google Scholar
  22. Mashkovsky MD, Grinev AN, Andreeva NI, Altukhova LB, Shvedov VI, et al. A new antidepressant drug — pirazidole. Khimiko-Farmatsevticheskii Zhurnal 33: 60–61, 1974Google Scholar
  23. Medvedev AE, Rajgorodskaya DI, Gorkin VZ, Fedotova IB, Semiokhina AF. The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain: focus on chemical pathogenesis of experimental audiogenic epilepsy. Molecular and Chemical Neuropathology 16: 187–201, 1992PubMedCrossRefGoogle Scholar
  24. Nikushkin EV, Kryzhanovsky GN. Lipid peroxidation in the development of epileptic activity. Patologicheskaia Fiziologiia i Eksperimentalnaia Terapiia 3: 19–24, 1987Google Scholar
  25. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 95: 351–358, 1979PubMedCrossRefGoogle Scholar
  26. Snyder SH. Drug and neurotransmitter receptors. New perspectives with clinical relevance. Journal of the American Medical Association 261: 3126–3129, 1989PubMedCrossRefGoogle Scholar
  27. Veryovkina IV, Abdel Samed MM, Gorkin VZ. Mitochondrial monoamine oxidase of rat liver: reversible qualitative alterations in catalytic properties. Biochimica et Biophysica Acta 258: 56–70, 1972PubMedCrossRefGoogle Scholar
  28. Veryovkina IV, Asnina VV, Gorkin VZ, Mashkovsky MD. Selective inhibition by pirazidole of monoamine oxidases of the type A in various human and animal tissues. Voprosy Meditsinskoi Khimii 5: 118–123, 1983Google Scholar

Copyright information

© Adis International Limited 1992

Authors and Affiliations

  • A. Medvedev
    • 1
  • V. Gorkin
    • 1
  • V. Shvedov
    • 2
  • O. Fedotova
    • 2
  • I. Fedotova
    • 3
  • A. Semiokhina
    • 3
  1. 1.Institute of Biological and Medical ChemistryAcademy of Medical SciencesMoscowRussia
  2. 2.Centre of Drug Chemistry - the All-Union Institute of Pharmaceutical ChemistryMoscowRussia
  3. 3.Biological FacultyMV Lomonosov State UniversityMoscowRussia

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