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Pharmacological analysis of the central cardiovascular effects of four GABA analogues

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Summary

The central cardiovascular effects of 4 structural analogues of GABA were investigated. The drugs were injected intracerebroventricularly (i.c.v.) in cumulative doses into pentobarbital-anaesthetized normotensive rats. Muscimol (0.01–10 μg/kg), THIP (0.01–100μg/kg), kojic amine (0.1–100 μg/kg) and isoguvacine (0.1–100μg/kg) produced dose-dependent hypotension and bradycardia. The maximal fall in the mean blood pressure was of about 35% of the initial values. These effects appears to be of central origin since the intravenous (i.v.) injection of the same doses of the drugs did not produce any similar cardiovascular modifications. The hypotensive effects of muscimol and kojic amine were antagonized partly by i.c.v. bicuculline. The combination of bicuculline and kainic acid almost completely prevented the blood pressure lowering effects of muscimol, kojic amine and isoguvacine. THIP however was only slightly antagonized by bicuculline and kainic acid. Atropine i.v. also prevented partly the cardiovascular effects of all these drugs.

Thus, the mechanisms of the central cardiovascular actions of GABA analogues appear to be more complex than expected and variable from one drug to another.

The involvement of GABA receptors of the A and B types and of cholinergic mechanisms in the hypotensive effect of the drugs is discussed.

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Authors and Affiliations

  1. Faculté de Médecine, Institut de Pharmacologie, 11 rue Human, F-67000, Strasbourg, France

    Pascal Bousquet, Josiane Feldman, Roger Bloch & Jean Schwartz

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  1. Pascal Bousquet
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  2. Josiane Feldman
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  3. Roger Bloch
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  4. Jean Schwartz
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Bousquet, P., Feldman, J., Bloch, R. et al. Pharmacological analysis of the central cardiovascular effects of four GABA analogues. Naunyn-Schmiedeberg's Arch. Pharmacol. 325, 291–297 (1984). https://doi.org/10.1007/BF00504371

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  • DOI: https://doi.org/10.1007/BF00504371

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