title: Cardiac electrophysiologic action of carteolol hydrochloride (OPC-1085), a new beta-adrenergic blocking agent.
abstract: Cardiac electrophysiologic action of a new beta-adrenergic blocking agent carteolol hydrochloride, or OPC-1085, was studied in either isolated, perfused rabbit hearts or in atrial, ventricular or Purkinje fibers of dogs and rabbits superfused in the tissue bath. Transmembrane potentials were recorded with intracellular microelectrodes and atrioventricular conduction was studied by recording a His bundle electrogram. OPC-1085 at a concentration of 0.1 mg/L shortened the sinus node recovery time, while propranolol at a comparable concentration prolonged it. Isoproterenol-enhanced canine Purkinje automaticity was more markedly depressed by OPC-1085 than by propranolol. In rabbit atrial and ventricular muscle, OPC-1085 up to the concentration of 2 mg/L did not alter the action potential characteristics but tended to shorten the conduction time. At 20 mg/L, OPC-1085 significantly decreased the maximal rate of depolarization and maximal following frequency, and prolonged the action potential duration and conduction time in non-reserpinized as well as reserpinized preparations. On atrioventricular conduction, 0.1 mg/l to 5mg/L of this drug prolonged the St-A and H-V intervals but tended to shorten the A-H interval. All these intervals were prolonged at 20 mg/L. The action potential duration of canine Purkinje-ventricular block developed at higher frequencies of stimulation. In view of the clinical dosage levels, it is sugg ested that the antiarrhythmic effects of OPC-1085 depend predominantly on its beta blocking action. At higher concentrations, OPC-1085 may exert some beta stimulating action, whereas still higher and possibly toxic concentrations could depress conduction through a direct membrane effect.
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D002036:Bundle of His; D002354:Carteolol / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects*; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects
chemical_list: D011412:Propanolamines; D012110:Reserpine; D002354:Carteolol; D011433:Propranolol; D007545:Isoproterenol