METABOLIC DIFFERENCES OF STRYCHINE IN THE RAT IN RELATION TO SEX

Abstract

In the previous paper, the remarkable difference in strychnine toxicity between adult female and adult male rats was reported (1). This sex difference is observed in cases of intraperitoneal, subcutaneous or oral administration of the drug but not by intravenous injection. After pretreatment with SKF 525 A such sex difference also disappeared. The different capacities of breakdown of strychnine by liver of female and male rats were supposed to account for such sex difference. It is worth while for noticing that such remarkable sex difference in strychnine toxicity after intraperitoneal injection of the drugs takes place within 10 minutes. It has been generally considered that such short time is not enough to produce marked difference through metabolic processes, and a different sensitivity of central nervous system in both sexes was considered to be a responsible factor (2, 3). In recent time, the authors have demonstrated that there is a marked decrease of strychnine toxicity through an increase of strychnine metabolism by pretreatment (48 hours before) with phenobarbital, phenaglycodol, thiopental and glutethimide (4-6). These results suggested a rapid “in vivo” metabolism of strychnine which could produce a marked difference in the toxicity by a modification of metabolic rate. In this paper, the possibility of the presence of such sex difference in metabolism of strychnine between both sexes of rats was studied.