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.
Drago
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F
Department of Experimental and Clinical Pharmacology, University of Catania Medical School, Viale A. Doria 6, 95125, Catania, Italy. fdrago@tin.it
Frisina
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M
Grech
M
M
Nicolosi
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A
Micale
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V
Nicosia
A
A
Medico
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Foti
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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