Centrally Mediated Cardiovascular Effects of B-HT 920 (6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine dihydrochloride), A Hypotensive Agent of the “Clonidine Type”

Abstract

Intravenous injection of 30 micrograms/kg of B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine dihydrochloride) into cats lead initially to an increase in blood pressure and then to a long-lasting decrease in blood pressure and heart rate. The central site of the hypotensive and bradycardiac action was demonstrated by the significantly greater effect after intracisternal (i.ci.) than after intravenous injection of B-HT 920, 3 micrograms/kg. The drug decreased the rate of spontaneous discharges in preganglionic splanchnic nerve fibers of normal and noradrenaline-depleted cats (3 micrograms/kg, i.ci.). Vagally mediated reflex bradycardia elicited by angiotensin injection in beta-adrenoceptor-blocked dogs was facilitated by intracisternal injection of 10 micrograms/kg B-HT 920. Both sympathoinhibition and vagal reflex facilitation were antagonized by the alpha-adrenoceptor-blocking agent piperoxan (50 micrograms/kg, i.ci). Therefore, B-HT 920 can be classified as an agent of the clonidine type, despite its different chemical structure. Quantitative differences between B-HT 920 and clonidine are discussed with respect to the greater alpha 2/alpha 1 adrenoceptor activity ratio of the former drug, as reported previously.