MECHANISM OF NEUROTOXICITY OF CARDIOTONIC GLYCOSIDES

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Abstract
1In cats intracerebroventricular administration of 5, 10, 20 μg of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 μg of ouabain, produced marked neurotoxicity. This was dose-related. 2Prior administration of reserpine (2 mg/kg i.m., 500 μg i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/kg i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/kg i.p., 2 mg i.c.v.) and haloperidol (200 μg i.c.v.) were ineffective. 3Prior administration of 2-bromolysergic acid diethylamide (BOL-148, 200 μg i.c.v.) or p-chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain. 4Perfusion of the lateral ventricles of cats with 10, 20 and 30 μg of peruvoside or ouabain produced a massive release of 5-hydroxytryptamine (5-HT). This was dose-related. Prior administration PCPA suppressed the release of 5-HT. 5The results of the findings indicate the involvement of 5-HT in the genesis of neurotoxicity induced by peruvoside or ouabain.