The effect of olanzapine pretreatment on acute cocaine toxicity in mice.
BACKGROUND
Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model.


METHODS
Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine.


RESULTS
Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine.


CONCLUSIONS
In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.
Heard
Kennon J
KJ
Rocky Mountain Poison and Drug Center, Denver Health, Denver, CO 80204, USA. kennon.heard@rmpdc.org
Cleveland
Nathan R
NR
Krier
Shay
S
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004336:Drug Antagonism; D007274:Injections, Intraperitoneal; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000077152:Olanzapine; D011041:Poisoning / Q000517:prevention & control*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000633:toxicity*
D001569:Benzodiazepines; D003042:Cocaine; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors; D014662:Vasoconstrictor Agents