Effect of chlorpromazine and quinacrine on the lethality in mice of the venoms and neurotoxins from several snakes.
Antivenoms are the currently available agents for the treatment of intoxication by snake venoms. Therapeutic approaches using more generally available drugs could improve treatment of envenomation by reducing the cost of the therapeutic agent, eliminating hypersensitivity reactions to antivenoms, and reducing storage costs. I investigated the efficacies of chlorpromazine and quinacrine with respect to reducing the lethality in mice of Bungarus caeruleus venom, Bungarus multicinctus venom and its neurotoxic components alpha- and beta-bungarotoxin, Crotalus durissus terrificus venom and its neurotoxic component crotoxin, and Oxyuranus scutellatus venom and its neurotoxic component taipoxin. Venom or toxin was administered i.p., followed immediately by an i.p. injection of chlorpromazine or quinacrine. The effect of drug on the lethality of the venom was recorded 24 hr later. Chlorpromazine and quinacrine were effective antagonists of the lethality of B. caeruleus venom, B multicinctus venom, and beta-bungarotoxin without themselves being overtly toxic. Chlorpromazine (1 mg/kg) increased the LD50 of B. caeruleus venom, B. multicinctus venom, and beta-bungarotoxin by 8.6-, 2.6- and 3.7-fold, respectively. In the range of 1 to 5 mg/kg, quinacrine increased the LD50 of B. caeruleus venom, B. multicinctus venom and beta-bungarotoxin by 5.7-, 11- and 8.6-fold, respectively. Neither drug had any effect on the other venoms or toxins. Chlorpromazine and quinacrine were also injected at different times both before and after the injection of venom or toxin. Protection from lethality was maximal for both drugs when they were administered immediately after injection of venom or toxin.
Crosland
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Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21701-5011.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000633:toxicity; D011796:Quinacrine / Q000494:pharmacology*
D003435:Crotalid Venoms; D004546:Elapid Venoms; D009498:Neurotoxins; D010741:Phospholipases A; D011796:Quinacrine; D002746:Chlorpromazine