Effects of several drugs on the automaticity of blood-perfused canine sino-atrial node preparation were examined by injecting drugs into the sinus node artery. All drugs produced a dose-dependent decrease in sino-atrial rate, although dl-alprenolol in low doses produced a slight increase, and their relative potencies determined on the basis of the molar doses producing a decrease by 15 beats/min (ED 15) were in the descending order: SK&F24260 greater than or equal to nifedipine greater than or equal to adenosine greater than quinidine greater than dl-propranolol greater than or equal to dl-alprenolol greater than procaine, and 1:1/1.2:1/2.0:1/28.8:1/114.2:1/123.8:1/704.2. Potencies of dl- and d-alprenolol and propranolol in causing a negative chronotropic action were almost equal. In higher doses, SK&F24260 and nifedipine (3-10 microgram), quinidine (0.3-1 mg), dl-propranolol and alprenolol (0.3-1 mg), and procaine (1-3 mg) caused a sino-atrial arrest. The order of potency in causing arrest was approximately similar to that in causing arrest was approximately similar to that in causing a negative chronotropic action (ED 15). Adenosine showed a profound negative chronotropic effect but did not cause a sino-atrial arrest. The negative chronotropic action and sino-atrial arrest caused by dl- and d-alprenolol and propranolol, quinidine and procaine maybe due mainly to their calcium antagonistic properties, but it is considered that their action sites are individually different. Furthermore, we suggest that in conscious dogs the tachycardia produced by the systemic administration of dl-alprenolol is not entirely due to its intrinsic sympathomimetic effect.
Adenosine Alprenolol