COMPARISON OF NEWLY SYNTHESIZED β-ADRENERGIC BLOCKERS, OPC 1085 AND SQ 11725, WITH PINDOLOL AND PROPRANOLOL IN THE BLOOD-PERFUSED CANINE SA NODE AND PAPILLARY MUSCLE PREPARATIONS

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Abstract
All drugs were injected intraarterially in volumes of 10-30 .mu.l for 4 s. Norepinephrine was used as an agonist in doses of 0.1 (-) 1 nmol. Norepinephrine was given 1 min after the administration of the antagonist and every 10 min successively until complete recovery from the .beta.-adrenergic blocking effect. OPC 1085 [dl-5 (3-tert-butyl-amino-2-hydroxy) propoxy-3,4 dihydro-carbostyril hydrochloride] showed a sympathomimetic response like pindolol, but its .beta.-adrenergic blocking effect was more long-lasting. In doses sufficient to completely block the chronotropic and inotropic responses to 0.3-1 nmol of norepinephrine, its effect persisted over 2 h. SQ 11725 [dl-2,3-cis-1,2,3,4-tetrahydro-5-(2-hydroxy-3-tert-butylamino) propoxy-2,3-naphthalenediol] had practically no sympathomimetic effect. Its blocking effect disappeared within 1 h even in doses for inducing a complete blocking activity to 0.3-1 nmol of norepinephrine, which was shorter than that of propranolol. Dose-effect curves for these compounds to block the effect of norepinephrine in the sino-atrial node preparation and those in the papillary muscle preparation were shown. The potencies of these compounds at the peak effect were as follows: OPC 1085 > pindolol = SQ 11725 > propranolol.