Ziprasidone, diazepam, or the combination for prevention of cocaine toxicity in a mouse model.
BACKGROUND
Acute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.


OBJECTIVE
To assess whether the combination of these two medications would offer more protection than either treatment alone.


METHODS
This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.


RESULTS
All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).


CONCLUSIONS
This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures.
Cleveland
Nathan R
NR
Denver Health Residency in Emergency Medicine, University of Colorado School of Medicine, USA.
Krier
Shay
S
Heard
Kennon
K
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control*; D016001:Confidence Intervals; D003975:Diazepam / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010879:Piperazines / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013844:Thiazoles / Q000494:pharmacology*
D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone; D003042:Cocaine; D003975:Diazepam