The effect of SCH 23390 against toxic doses of cocaine, d-amphetamine and methamphetamine

Robert W. Derlet, Timothy E Albertson, Pam Rice

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 ≤ 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, suggest that different mechanisms of toxicity may exist between these drugs at high doses.

Original languageEnglish (US)
Pages (from-to)821-827
Number of pages7
JournalLife Sciences
Issue number9
StatePublished - 1990

ASJC Scopus subject areas

  • Pharmacology


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