Dual effects of melatonin on barbiturate-induced narcosis in rats.
Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action.
Department of Experimental and Clinical Pharmacology, University of Catania Medical School, Viale A. Doria 6, 95125, Catania, Italy. fdrago@tin.it
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Grech
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D000759:Adjuvants, Anesthesia / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001463:Barbiturates; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D014474:Unconsciousness / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality
D000759:Adjuvants, Anesthesia; D000778:Anesthetics, Dissociative; D000975:Antioxidants; D001463:Barbiturates; D007649:Ketamine; D008550:Melatonin; D003975:Diazepam