MECHANISM OF NEUROTOXICITY OF CARDIOTONIC GLYCOSIDES

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. 1977 British Pharmacological Society