EFFECT OF THE NEW BETA-ADRENOLYTIC COMPOUND YL-3-ACETYL-4[(2-HYDROXY-3-ISOPROPYLAMINO)PROPOXY] CARBANYLATE HYDROCHLORIDE ON ISOLATED HEART-MUSCLE

The effect of the newly beta-adrenolytic drug Bl 343 Ac l-3-acetyl-4-[ (2-hydroxy-3-isopropylamino)propoxy] carbanylate hydrochloride) was te sted in preparations of the guinea-pig atrium and compared with the ef fects of propranolol and metipranolol. Bl 343 Ac has an affinity to be ta-adrenergic receptors, expressed as the pA(2) value which is compara ble to those of propranolol and metipranolol. To achieve the slope of the Schild plot not different from unity, it was necessary, to prolong incubation of the drug with the tissue to 75 min. At the concentratio ns of 10(-5) and 10(-4) mol/l and higher; Bl 343 Ac was found to have negative chronotropic and inotr opic effects, respectively. In atria i solated from guineapigs and rats premedicated with reserpine, applicat ion of 10(-8) and 10(-7) mol/l of Bl 343 Ac exhibited a slightly stimu latory effect on the chronotropy. A positive inotropic effect of sl 34 3 Ac was observed on the left guinea-pig atria after prolongation of t he incubation time of the drug with the tissue lip to 75 min. This ino tropic effect of Bl 343 Ac may be associated with art increased concen tration of cyclic adenosine monophosphate (cAMP), observed after 1-h i ncubation with the drug (from 0.78 +/- 0.05 to 1.13 +/- 0.09 pmol/mg w .w. cAMP). Bl 343 Ac, similarly to propranolol and metipranolol, prolo nged the refractory period in the atrial preparations starting with th e concentration of 10(-6) mol/l. In the ventricular preparations, Bl 3 43 Ac shortened the refractory period up to the concentration of 10(-5 ) mol/l, similarly to propranolol. Metipranolol did not affect the ref ractory, period of the cardiac ventricle.