Mechanism of neurotoxicity of cardiotonic glycosides.
1 In cats intracerebroventricular administration of 5, 10, 20 mug of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 mug of ouabain, produced marked neurotoxicity. This was dose-related. 2 Prior administration reserpine (2 mg/kg i.m., 500 mug i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/,g i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/,g i.p., 2 mg 2.c.v.) and haloperidol (200 mug i.c.v.) were ineffective. 3 Prior administration of 2-bromolysergic acid diethylamide (BOL-148, 200 mug i.c.v.) or p-chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain. 4 Perfusion of the lateral ventricles of cats with 10, 20 and 30 mug of peruvoside or ouqbain produced a massive release of 5-hydroxytryptamine (5-HT). This was dose-related. Prior administration PCPA suppressed the release of 5-HT. 5 The results of the findings indicate the involvement of 5-HT in the genesis of neurotoxicity induced by peruvoside or ouabain.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002298:Cardenolides / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000008:administration & dosage / Q000009:adverse effects*; D002395:Catecholamines / Q000378:metabolism; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D004347:Drug Interactions; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D008094:Lithium / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D002298:Cardenolides; D002301:Cardiac Glycosides; D002395:Catecholamines; D012701:Serotonin; D010042:Ouabain; D008238:Lysergic Acid Diethylamide; D008094:Lithium; D006220:Haloperidol; D010134:Fenclonine