Cardiac effects of YM-09538, a new .ALPHA.- and .BETA.-adrenoceptor blocking agent, on SA nodal pacemaker activity and contractility in isolated atria and intact dogs.

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Abstract
The effects of a newly synthetic .alpha.- and .beta.-adrenoceptor blocking agent, YM-09538 [5-[1-hydroxy-2-[[2-(o-methoxyphenoxy)ethyl]amino]ethyl]-2-methylbenzenesulfonamide hydrochloride], on SA [sinoatrial] nodal pacemaker activity and contractility of atria and intact dogs were studied using isolated and blood-perfused canine atrial muscle preparations supported by a donor dog. Administration of YM-09538 (10-100 .mu.g/kg i.v.) caused hypotension without tachycardia, but was accompanied with bradycardia in anesthetized dogs. In these cases, the SA nodal pacemaker activity and atrial contractility in isolated atria was influenced little. This indicates that the concentration of YM-09538 that induces hypotension has no direct cardiac effects. Direct administration of YM-09538 to isolated atria caused dose-dependent negative chronotropic and inotropic effects, and the potency was 3-30 times less than that of propranolol. In electrically paced preparations, a large dose of YM-09538 produced a uniform depression of the developed tension at all frequencies examined (2-3 Hz). Verapamil caused a greater suppression of developed tension at higher frequencies, indicating that the mode of action of YM-09538 is different from that of verapamil.