Hormonal environment and age influencing the activity of flumecinol, a synthetic enzyme inducer

The synthetic inducer of m-trifluoromethyl-alpha-ethylbenzhydrol (flumecinol, Zixoryn) is described as a phenobarbital type inducer of microsomal mixed-function oxydases. We have studied in rats of either sex whether flumecinol action is related to sex, endogenous hormonal environment and age. The action of a single orally administered dosage of 40 ml/kg was analysed. The changes in hexobarbital narcosis, wet liver weight, microsomal protein content, cytochrome P-450 and cytochrome b5 concentrations were recorded. Signs of induction as shortened hexobarbital anaesthesia, increased wet liver weight and microsomal protein as well as cytochrome P-450 content are characteristic, however, NADH-cytochrome b5 system participating in inductive process is also possible. We observed a well developed inducing activity in young females. There were no cyclic differences during sexual cycle. In old animals efficacy decreased. Following ovariectomy, flumecinol exerted inhibiting effect on microsomal oxydases. Induction observed in young males increased in old animals. In orchidectomised rats inhibiting effect developed. Inducing potency of flumecinol is more pronounced in females than in males. In the absence of sexual steroids an adverse reaction developed in both sexes, nevertheless, stronger in females. Aging decreased induction in females although cycling was regular. In males of advanced age inducing activity was more pronounced likewise to phenobarbital induction.