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

Abstract
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.
AuthorsR W Derlet, T E Albertson, P Rice
JournalLife sciences (Life Sci) Vol. 47 Issue 9 Pg. 821-7 ( 1990) ISSN: 0024-3205 [Print] Netherlands
PMID2215083 (Publication Type: Journal Article)
Chemical References
  • Benzazepines
  • Methamphetamine
  • Cocaine
  • Dextroamphetamine
Topics
  • Animals
  • Benzazepines (pharmacology)
  • Cocaine (antagonists & inhibitors, toxicity)
  • Dextroamphetamine (antagonists & inhibitors, toxicity)
  • Dose-Response Relationship, Drug
  • Male
  • Methamphetamine (antagonists & inhibitors, toxicity)
  • Rats
  • Rats, Inbred Strains
  • Seizures (chemically induced, prevention & control)

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