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Effects of the new beta-adrenoceptor blocking agent, S-596 on the peripheral autonomic nervous system and smooth muscles.

The effects of the new beta-adrenoceptor blocking agent, S-596, on the peripheral autonomic nervous system and smooth muscles were studied in comparison with propranolol. In urethane or alpha-chloralose anesthetized cats S-596 (10 micrograms/kg, i.v.) antagonized the cardiovascular responses induced by isoproterenol. S-596, in doses ranging from 100 to 300 micrograms/kg (i.v.) reduced the contractions of the nictitating membrane induced by electrical stimulation of preganglionic and postganglionic fibers to the superior cervical ganglion. Higher doses of S-596 were required to depress the effects of noradrenaline and tyramine. In spinal cats the tyramine and noradrenaline dose-response curve was shifted to the right by S-596. In isolated rat aortic strips S-596 displaced the noradrenaline dose-response curve to the right in a parallel fashion indicating a competitive antagonism. Its potency was about one tenth of that of phentolamine. These results suggest that S-596 possesses both alpha-and beta-adrenoceptor blocking activities.