The effect of SCH 23390 against toxic doses of cocaine, d-amphetamine and methamphetamine.
The effect of SCH 23390, a dopamine-one (D1) antagonist, in preventing acute toxicity induced by lethal doses of cocaine, d-amphetamine, and methamphetamine was studied in the rat. Animals were first pretreated with SCH 23390 (0.0, 0.5, 1.0, and 2.5 mg/kg, i.p.) and then were challenged with cocaine (70 mg/kg, i.p., an LD85), d-amphetamine (75 mg/kg, i.p., an LD95), and methamphetamine (100 mg/kg, i.p., an LD90). SCH 23390 did not alter the incidence of stimulant-induced seizures compared to the vehicle controls. Significant protection against cocaine-induced death was afforded only by the lowest dose of SCH 23390 tested. Significant protection against d-amphetamine-induced death was provided by all doses, with a dose dependent effect noted so that the incidence decreased from 95% for vehicle to 30% (p less than or equal to 0.01) with 2.5 mg/kg SCH 23390 pretreatment. No statistically significant reduction in the incidence of methamphetamine-induced death was seen with SCH 23390 pretreatment. The ability of SCH 23390 to protect against d-amphetamine, but apparently not against methamphetamine-induced death, suggests that different mechanisms of toxicity may exist between these drugs at high doses.
Derlet
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Department of Internal Medicine, University of California, School of Medicine, Davis 95616.
Albertson
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Rice
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D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D001552:Benzazepines; D008694:Methamphetamine; D003042:Cocaine; D003913:Dextroamphetamine