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Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone

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The effects of methaqualone on isonicotinic acid hydrazide, 6-mercapto propionic acid, picrotoxin, and strychnine-induced convulsion were studied in mice and the results compared with diazepam. Methaqualone, like diazepam, was found to be a selective antagonist of isoniazid-induced convulsion and a much less effective inhibitor of strychnine convulsion.

Methaqualone elicits muscle-relaxant, sedative, and anticonvulsant effects at different dose levels. At low, nonsedative doses the drug produces anticonvulsant effects, and at higher doses, muscle-relaxant and sedative effects. It appears that the mechanism(s) of action of methaqualone is on GABA deficiency or receptor blockade, rather than on glycine receptors.

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  1. Corrodi, H., Fuxe, K., Lidbrink, P., Olson, L.: Minor tranquillisers, stress and central catecholamine neurons. Brain Res. 29, 1–16 (1971)

  2. Costa, E., Guidotti, A., Mao, C. C.: Evidence for involvement of GABA in the action of benzodiazepines: studies on rat cerebellum. In: Advances in biochemical psychopharmacology 14, E. Costa and P. Greengard, eds. pp. 113–130. New York: Raven 1975a

  3. Costa, E., Guidotti, A., Mao C. C., Suria, A.: New concepts on the mechanism of action of Benzodiazepines. Life Sci. 17, 167–186 (1975b)

  4. Costa, E., Guidotti, A., Mao, C. C.: Diazepam, cyclic nucleotides and amino acid neurotransmitters in rat cerebllum. CINP meeting, Paris, France, pp. 849–855 (1975c)

  5. Curtis, D. R., Johnston, G. A. R.: Amino acid transmitters in mammalian central nervous system. Rev. Physiol. Biochem. Exp. Pharmacol. 69, 97–188 (1974)

  6. Dews, P. B.: The measurement of the influence of drugs on voluntary activity in mice. Br. J. Pharmacol. 8, 46–48 (1953)

  7. Doteuchi, M., Costa, E.: Pentylenetetrazol convulsions and brain catecholamine turnover rate in rats and mice receiving diphenyl hydanatoin or benzodiazepines. Neuropharmacology 12, 1059–1072 (1973)

  8. Haefely, W., Kulcsar, A., Mohler, H., Pieri, L., Polc, P., Schafferer, R.: Possible involvement of GABA in the central actions of benzodiazepines. In: Advances in biochemical psychopharmacology 14, E. Costa and P. Greengard, eds., pp. 131–151. New York: Raven 1975

  9. Julien, R. M.: Cerebellar involvement in the anti-epileptic action of Diazepam. Neuropharmacology 11, 683–691 (1972)

  10. Kaim, S. C., Rosentein, I. N.: Diseases of the nervous system. [Suppl.] 21, 46–48 (1960)

  11. Kinnard, W. J., Jr., Carr, J.: A preliminary procedure for the evaluation of central nervous system depressants. J. Pharmacol. Exp. Ther. 121, 354–361 (1957)

  12. Ladinsky, H., Consolo, S., Peri, G., Garattini, S.: Increase in mouse and rat brain acetylcholine levels by diazepam in benzodiazepines, S. Garattini, E. Mussini, and L. O. Randall, eds., pp. 241–242. New York: Raven 1973

  13. Litchfield, J. T., Wilcoxon, F. A.: A simplified method of evaluating dose effect experiments. J. Pharmacol. Exp. Ther. 96, 99–113 (1949)

  14. Lores Arnaiz Georgina Rodriguez de Blanca Rogiolo de Esteves, Marta Mistrorigo de Pacheco: Inhibition in vitro of protein synthesis in brain subcellular fractions by the convulsant 3-mercapto propionic acid. Biochem. Pharmacol. 24, 2307–2309 (1975)

  15. Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with Folin Phenol reagent. J. Biol. Chem. 193, 265–275 (1951)

  16. Mao, C. C., Guidotti, A., Costa, E.: Interactions between gamma aminobutyric acid and guanosine cyclic 3′, 5′ monophosphate in rat cerebellum. Mol. Pharmacol. 10, 736–745 (1974)

  17. Mao, C. C., Guidotti, A., Costa, E.: Evidence for an involvement of GABA in the mediation of the cerebellar cyclic GMP decrease and the anti-convulsant action of diazepam. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 369–378 (1975a)

  18. Mao, C. C., Guidotti, A., Costa, E.: Inhibition by diazepam of the turnover and the increase of cyclic GMP content elicited by harmaline. Brain Res. 83, 516–519 (1975b)

  19. Naik, S. R., Guidotti, A., Costa, E.: Central GABA receptor agonist comparison of muscimol and baclofen. Neuropharmacology 15, 479–484 (1976)

  20. Okada, Y., Nitsch-Hassler, C., Kim, J. S., Bak, I. J., Hassler, R.: Role of gamma aminobutyric acid (GABA) in the extrapyramidal motor system. One regional distribution of GABA in rabbit, rat, guinea pig and baboon C.N.S.. Brain Res. 13, 514–518 (1971)

  21. Polc, P., Mohler, H., Haefely, W.: The effect of diazepam on spinal cord activities. Possible sites and mechanisms of action. Arch. Pharmacol. 284, 319–337 (1974)

  22. Schlosser, W.: Action of diazepam on the spinal cord. Arch. Int. Pharmacodyn. 194, 93–102 (1971)

  23. Schmidt, R. F.: Presynaptic inhibition in the vertebrate central nervous system ergebaisse der Physiol. Biol. Chem. Exp. Pharmakol. 63, 20–101 (1971)

  24. Schmidt, R. F., Vogel, M. E., Zimmermann, M.: Die Wirkung von Diazepam auf die präsynaptische Hemmung und andere Rückenmarksreflexe. Arch. Pharmacol. 258, 69–82 (1967)

  25. Stein, L., Wise, C. D., Berger, B. D.: Anti-anxiety action of benzodiazepines. Decrease in activity of serotonin neurones in the punishment system. In: The benzodiazepines, S. Garattini, ed., pp. 299–326. New York: Raven 1973

  26. Swift, J. G., Dickens, E. A., Backer, B. A.: Anti-convulsant and other pharmacological activities of tuazolone [2-methyl-3-Otolyl-4 (3H)] quinazolone. Arch. Int. Pharmacodyn. 128, 112–115 (1960)

  27. Wittenborn, J. R.: The clinical psychopharmacology of anxiety. Springfield, Ill: Thomas 1966

  28. Wood, J. D., Peeskar, S. J.: The role of GABA metabolism in the convulsant and anti-convulsant actions of amino-oxyacetic acid. J. Neurochem. 20, 379–387 (1973)

  29. Young, A. B., Zukin, S. R., Snyder, S. H.: Interaction of benzodiazepines with central nervous system glycine receptor possible mechanism of action. Proc. Nat. Acad. Sci. 71, 2246–2250 (1974)

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Naik, S.R., Naik, P.R. & Sheth, U.K. Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone. Psychopharmacology 57, 103–107 (1978). https://doi.org/10.1007/BF00426965

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Key words

  • Isonicotinic acid hydrazide
  • 6-Mercapto propionic acid
  • Picrotoxin
  • strychnine
  • Convulsion
  • GABA