THE PRODUCTION OF POIKILOTHERMIA IN MICE BY OXAZOLE QUATERNARY SALTS

¹ Biomedical Research Group, Health Division, Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico

A casual observation that mice given an oxazole quaternary salt intraperitoneally became cold led to an investigation in which 17 related oxazolium tosylates were synthesized, their toxicity determined and their effect upon thermoregulatory efficiency tested. Two compounds stood out as being potent inhibitors of the temperature regulating ability of mice, i.e. 2-(4-methoxyphenyl)- 3-methyl-5-phenyloxazolium tosylate and 2-(1-naphthyl)-3-methyl-5-phenyloxazolium tosylate. Mice given these compounds intraperitoneally in doses of 100 mgm. per kgm. of body weight were no longer homeothermic. The duration and extent of the chemically-induced poikilothermic state were directly proportional to the dose. Recovery occurred slowly, starting about four hours after injection. The body temperature after administration of the effective compounds was shown to be determined by the temperature of the environment. There was indirect evidence for a specific action of the compounds upon the central nervous system. When tested in rabbits with pyrogen-induced hyperpyrexia, the drugs had a pronounced antipyretic action.