Effects of brotizolam on cardiovascular functions and autonomic nervous system

The effects of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-fl-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin), a new thieno-triazolo-diazepine, on the heart, hemodynamic functions and the autonomic nervous system were investigated in rats, guinea pigs, rabbits, cats and dogs: In pentobarbital anesthetized dogs, 1 or 5 mg/kg brotizolam administered intravenously, decreased heart rate, with a frequency-dependent prolongation of the intervals and heightening of the T-waves in the electrocardiogram, depressed respiration, whereas the blood pressure was unaffected. In urethane anesthetized rabbits, 5 or 10 mg/kg brotizolam intravenously had almost no distinct effect on blood pressure and heart rate, though it slightly decreased respiratory rate at 10 mg/kg. In nonanesthetized rabbits, brotizolam exerted similar actions on respiration, blood pressure and heart rate. In isolated guinea pig atria, 1-10 mg/l brotizolam did not show noticeable effects on contractile force but decreased slightly the pulse rate. In pentobarbital anesthetized dogs, vertebral and carotid blood flow remained almost unchanged after 0.05 mg/kg brotizolam intravenously, but were increased following 0.5 mg/kg. Cardiac output and coronary flow were not changed by 0.5 mg/kg brotizolam but slightly decreased accompanied by a decrease in blood pressure and heart rate by 1 mg/kg. Femoral flow was not affected by 0.5 or 1 mg/kg. After 5 mg/kg brotizolam given intravenously in dogs, the pressor effect of epinephrine was significantly enhanced and the positive chronotropic effect increased to a certain degree. Both effects of norepinephrine also tended to be enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)