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 sub stances, 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 antago nists 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 temper ature 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. MATERIALS AND METHODSFor experiments on body temperature, adult male Sprague-Dawley rats weighing 150-230 g were used and kept in separate cages. The animals were kept in a thermosta tically controlled room at 22±10C for at least 24 hours before experiments. Diets were removed 12 hours before experiments and water was removed during experiments. Ani mals with a mean temperature of less 37.5°C were not used. The rectal temperature was measured at 30 or 60 minute intervals with a probe thermometer inserted 4 cm into the rectum and as a rule data are represented as the mean temperature of 7 to 10 animals.Analgesics were injected subcutaneously into rats 30 minutes before, or at the same time as Diazo-ICA or related compounds. For the writhing test, male ddO strain mice,