Effect of the new beta-adrenolytic compound propyl-3-acetyl-4-[(2-hydroxy-3-isopropylamino) propoxy]carbanylate hydrochloride on isolated heart muscle.

The effect of the new beta-adrenolytic drug Bl 343 Ac (propyl-3-acetyl-4-[(2-hydroxy-3-isopropylamino) propoxy] carbanylate hydrochloride) was tested in preparations of the guinea-pig atrium and compared with the effects of propranolol and metipranolol. BL 343 Ac has an affinity to beta-adrenergic receptors, expressed as the pA2 value, which is comparable 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 concentrations of 10(-5) and 10(-4) mol/l and higher, BL 343 Ac was found to have negative chronotropic and inotropic effects, respectively. IN atria isolated from guinea-pigs and rats premedicated with reserpine, application of 10(-8) and 10(-7) mol/l of Bl 343 Ac exhibited a slightly stimulatory effect on the chronotropy. A positive inotropic effect of Bl 343 Ac was observed on the left guinea-pig atria after prolongation of the incubation time of the drug with the tissue up to 75 min. This inotropic effect of Bl 343 Ac may be associated with an increased concentration of cyclic adenosine monophosphate (cAMP), observed after 1-h incubation 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, prolonged the refractory period in the atrial preparations starting with the concentration of 10(-6) mol/l. In the ventricular preparations, Bl 343 Ac shortened the refractory period up to the concentration of 10(-5) mol/l, similarly to propranolol.