[Mechanism of methamphetamine toxicity in grouped mice and the effects of centrally acting drugs on its toxicity (author's transl)].
The mortality of ddK mice treated with 40 mg/kg i.p. of methamphetamine (MA) was 85% in grouped conditions (10 mice in a cage) and 3% in individually isolated conditions. This mortality was not altered by the social environments even when other mice in the cage were not treated with MA. The mortality of mice individually isolated in cages with transparent walls was significantly higher than that of completely isolated mice. Almost all neuroleptics dose-dependently antagonized the MA toxicity in grouped mice, in small doses. The antagonizing activity of clozapine was somewhat weak, and sulpiride potentiated MA toxicity. Phentolamine and propranolol antagonized the MA toxicity at higher doses than neuroleptics. Reserpine and tetrabenazine previously given to mice remarkably antagonized the MA toxicity. H44/68 (a tyrosine hydroxylase inhibitor) had a considerable effect in antagonizing the MA toxicity, but diethyldithiocarbamate, U-14, 624 and FLA 63 (dopamine-beta-hydroxylase inhibitors) prevented the MA toxicity to a lesser extent than did H44/68. Apomorphine had no effect on the MA toxicity. The present data show that the MA toxicity in grouped mice (the increase in mortality) was enhanced by the presence of other mice, and suggest that the norepinephrine neurons play an important role in promoting the MA toxicity. Neuroleptics antagonize MA toxicity probably by blocking alpha-receptors in the central nervous system.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D012931:Social Environment; D014149:Tranquilizing Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D014149:Tranquilizing Agents; D008694:Methamphetamine