BIOLOGICAL ACTIVITIES OF DIAZONIUM COMPOUNDS: INDUCTION OF HYPOTHERMIA OR WRITHING BY 4 (OR 5)-DIAZOIMIDAZOLE-5 (OR 4)-CARBOXAMIDE AND THEIR ANTAGONISM BY ANALGESICS

Abstract

Siegmund et al. (1), Hendershot and Forsaith (2) and Vander Wende and Margolin (3) first described a syndrome, commonly referred to as “writhing”, which was induced in rodents by the intraperitoneal injection of various chemical agents. Collier et al. (4) have recently reported experiments on the abilities of various substances, including some occurring in tissues and causing pain in man, to induce abdominal construction in mice.
Many investigators have described the non-specificity of the writhing syndrome, this phenomenon being blocked or antagonized by non-narcotic, and narcotic antagonists as well as narcotic analgesics. The inhibition of drug-induced writhing in mice has been proposed as a screening test for analgesics (1, 2, 5-7), although non-analgesic drugs also inhibit writhing (2, 8, 9).
In the present experiments, intraperitoneal injection of the diazonium compound, 4 (or 5)-diazoimidazole-5 (or 4)-carboxamide had a profound effect on body temperature and induced the writhing syndrome. Both the severe hypothermia and writhing following its inejction could be ameliorated with analgesics. The mechanism on these effect are discussed.