Potentiation of cocaine toxicity with calcium channel blockers.
Three calcium channel blockers were studied for efficacy in preventing seizures and death from cocaine intoxication. Rats were first pretreated with a test drug then subjected to high dose intraperitoneal cocaine. In this model, control animals developed seizures within six minutes, followed by death within ten minutes. Animals that were pretreated with diltiazem, nifedipine, or verapamil developed seizures significantly faster than controls, and at specific doses the death rate was higher than in controls for all three drugs. The potentiation of seizures and death by 2 mg/kg nifedipine pretreatment was further shown by challenge with three different doses of cocaine. This study fails to demonstrate a protective effect and suggests augmentation of cocaine toxicity by pretreatment with the three currently available calcium channel blockers. Several mechanisms by which calcium channel blockers may augment cocaine-induced toxicity are discussed.
Derlet
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RW
Division of Emergency Medicine and Clinical Toxicology, University of California, Davis, Medical Center, Sacramento 95817.
Albertson
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TE
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D004110:Diltiazem / Q000009:adverse effects* / Q000627:therapeutic use; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D008297:Male; D009543:Nifedipine / Q000009:adverse effects* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced; D014700:Verapamil / Q000009:adverse effects* / Q000627:therapeutic use
D014700:Verapamil; D004110:Diltiazem; D003042:Cocaine; D009543:Nifedipine