EFFECTS OF TOBORINONE (OPC-18790), A NEW POSITIVE INOTROPIC AGENT, ONACTION-POTENTIAL IN GUINEA-PIG SINOATRIAL NODE - COMPARED WITH MILRINONE AND E-4031

The effects of toborinone 3,4-dimethoxybenzylamino)-2-hydroxypropoxy]- 2(1H)- quinolinone], OPC-18790), milrinone and E-4031 6-methyl-2-pyrid il)-1-ethyl)-4-(4-methanesulfonyl- amino-l-benzoyl)piperidine dihydroc hloride) on membrane potential were examined in isolated guinea pig si noatrial node preparations. Toborinone, a new positive inotropic agent , prolonged cycle length (CL), depolarized maximum diastolic potential (MDP) and decreased maximum upstroke velocity (V-max) and action pote ntial amplitude (APA). On the other hand, milrinone, a peak III phosph odiesterase (PDE III) inhibitor, increased V-max and AfA and shortened CL and action potential duration. E-4031, an I-K blocker, prolonged C L, depolarized MDP and decreased V-max and APA. These results suggest that toborinone modulates the action potential like an I-K blocker rat her than a PDE III inhibitor in a sinoatrial node.