The lethal effects of ethanol and cocaine and their combination in mice: implications for cocaethylene formation.
The HS line of mice was used to determine the LD50 values for cocaine and ethanol, as well as for cocaethylene, the enzymatic product of their coadministration. The LD50 of cocaethylene was found to be significantly lower than that of cocaine, and both were more potent in their lethality than ethanol. When a low-lethality dose of cocaine was administered with a nonlethal dose of ethanol, the result was a significant increase in the prevalence of lethality. Thus, the lethal effects of the dose of cocaine used were increased by the dose of ethanol administered such that the two drugs in combination were equipotent to cocaethylene. The results are discussed in light of the ability of the liver, via transestification, to rapidly form cocaethylene from cocaine in addition to ethanol's ability to decrease the catabolism of cocaine. Thus, the possibility exists that the increased lethality observed is produced by both the production of the more lethal cocaethylene and sustained levels of cocaine.
Schechter
M D
MD
Department of Pharmacology, Northeastern Ohio Universities, College of Medicine, Rootstown 44272, USA.
Meehan
S M
SM
D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D012727:Sex Characteristics
D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D000431:Ethanol; C066444:cocaethylene; D003042:Cocaine