Antagonism of cocaine, amphetamine, and methamphetamine toxicity

Robert W. Derlet, Timothy E Albertson, Pam Rice

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55 Scopus citations

Abstract

The effect of diazepam, haloperidol, MK-801, and propranolol in antagonizing behavioral symptoms induced by lethal doses of cocaine, amphethamine, and methamphetamine were studied in a rat model. Animals were first pretreated IP with potential antagonists, diazepam (2, 5, and 10 mg/kg), haloperidol (5, 10, and 20 mg/kg), propranolol (5, 10, and 20 mg/kg), MK-801 (0.5, 1.0, and 2.5 mg/kg), and then were challenged IP with cocaine (70 mg/kg) (LD85), d-amphethamine (75 mg/kg) (LD100), and methamphetamine (100 mg/kg) (LD90). Diazepam, at all doses, provided significant protection against cocaine- (p≤0.01) and methamphetamine- (p≤0.05) induced seizures and produced a dose-dependent effect against amphetamine-induced seizures. MK-801, at all doses, reduced seizures in all groups (p≤0.01). Propranolol altered the incidence of methamphetamine-induced seizures. Significant protection against cocaine-induced death was afforded by diazepam (p≤0.01) and propranolol (p≤0.05). Significant protection against amphetamine-induced death was provided by haloperidol (all doses, p≤0.1), MK-801 (all doses, p≤0.1), and propranolol (10 and 20 mg/kg, p≤0.1). No agent reduced the incidence of methamphetamine- (50 or 100 mg/kg) induced death. The failure of d-amphetamine antagonists to protect against methamphetamine-induced toxicity and death suggest that different mechanisms of toxicity may exist between these drugs.

Original languageEnglish (US)
Pages (from-to)745-749
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume36
Issue number4
DOIs
StatePublished - 1990

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Keywords

  • Amphetamine
  • Cocaine
  • Diazepam
  • Haloperidol
  • Methamphetamine
  • MK-801
  • Propranolol

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

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