The role of catecholamines in cocaine toxicity: A model for cocaine 'sudden death'

Berend Mets, Subhash Jamdar, Donald Landry

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Sudden death associated with cocaine abuse is preceded by a state of agitated delirium. We postulated that release of catecholamines associated with this stress enhanced toxicity from cocaine. Thus we investigated the effect of catecholamine infusion [(epinephrine (7.25 ugml-1), norepinephrine (4.4 ugml-1) and dopamine (8.0 ugml-1), infused at 6 ml h-1] on the toxicity from concomitant infusion of cocaine (1 mg-kg-1min-1). Two groups of rats were studied in order to isolate distinct toxicity endpoints: convulsions and respiratory arrest in conscious, and, circulatory arrest in anesthetized and ventilated rats. Catecholamines were administered at either full or 1/4 strength to establish a dose response effect on cocaine toxicity. Catecholamine infusion in a dose dependent fashion provoked earlier convulsions and respiratory arrest in conscious rats and circulatory arrest in anesthetized and ventilated rats. Despite lower cocaine cumulative dose administration, rats receiving catecholamines had similar plasma cocaine concentrations at the onset of convulsions and respiratory arrest compared to those with cocaine infusion alone. The data suggest that catecholamines enhance the convulsive, respiratory and circulatory toxicity of cocaine by a pharmacokinetic interaction.

Original languageEnglish (US)
Pages (from-to)2021-2031
Number of pages11
JournalLife Sciences
Volume59
Issue number24
DOIs
StatePublished - Nov 8 1996

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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