Cardiovascular pharmacology of ASL-8052, an ultra-short acting beta blocker

ASL-8052, a novel ultra-short acting beta receptor blocking agent, was infused i.v. and its cardiovascular effects were investigated in conscious, as well as anesthetized rabbits. On i.v. infusion, its effects reached a steady state within 6 min and on termination of infusion, complete recovery occurred within 20 min. In conscious rabbits it inhibited isoproterenol-induced tachycardia and hypotension. There was more pronounced inhibition of the cardioaccelerator effects of isoproterenol than its hypotensive effects. ASL-8052 produced dose dependent bradycardia in conscious rabbits which was more marked in rabbits pretreated with atropine methyl nitrate. When infused in larger doses, a significant decrease in mean arterial pressure was seen in conscious as well as anesthetized rabbits. This hypotensive effect was not blocked by prior beta receptor blockade with propranolol. ASL-8052-induced hypotension was found to be due to a significant decrease in total peripheral resistance. It also produced vasodilation in the mesenteric vascular bed. The role of the liver in the clearance of ASL-8052 was investigated. When infused into the portal vein, the response to ASL-8052 was markedly attenuated, while an equivalent dose infused into the femoral vein produced a significant level of beta receptor blockade. These results suggest that ASL-8052 is an ultra-short acting beta receptor blocking agent with vasodilator effects in rabbits. While the liver may play a significant role in the clearance of ASL-8052 from circulation, the role of extra-hepatic mechanisms in the rapid decay of its pharmacological effects remains to be investigated.