Effects of some benzodiazepine derivatives on fibrinolysis and serum lipids in normolipidaemic rats and in humans

Abstract

The effects of diazepam, chlordiazepoxide, lorazepam and bipotassium chlorazepate on the dilute blood-clot lysis time in normolipidaemic rats and in humans were investigated. Diazepam in small doses induced in acutely treated rats an acceleration of fibrinolysis. At the same time chlordiazepoxide was ineffective, while lorazepam and bipotassium chlorazepate delayed the lysis time. Large doses of diazepam were less effective than small ones, while chlordiazepoxide was more active when larger doses were used. Lorazepam had an inhibitory effect when administered in large doses. In contrast to the lowering effect exhibited by small doses of bipotassium chlorazepate, larger doses were found to produce a slight acceleration of lysis time. In subacutely treated rats, both small and large doses were found to activate fibrinolysis, with the exception of large doses of bipotassium chlorazepate which proved to be inhibitory. Only minor changes in serum lipids (total cholesterol and triglycerides) were observed in normolipidaemic rats treated with the compounds mentioned above. Acceleration of clot lysis but no significant changes in serum lipids or of plasma fibrinogen were noted in 13 healthy human volunteers given therapeutic doses of diazepam.