Effects of Toborinone (OPC-18790), a New Positive Inotropic Agent, on Action Potential in Guinea Pig Sinoatrial Node: Compared with Milrinone and E-4031

Abstract

The effects of toborinone ([(±)-6-[3-(3, 4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolinone], OPC-18790), milrinone and E-4031 (1-(2-(6-methyl-2-pyridil)-1-ethyl)-4-(4-methanesulfonyl-amino-1-benzoyl)piperidine dihydrochloride) on membrane potential were examined in isolated guinea pig sinoatrial 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 potential amplitude (APA). On the other hand, milrinone, a peak III phosphodiesterase (PDE III) inhibitor, increased V_max and APA and shortened CL and action potential duration. E-4031, an I_K blocker, prolonged CL, depolarized MDP and decreased V_max and APA. These results suggest that toborinone modulates the action potential like an I_K blocker rather than a PDE III inhibitor in a sinoatrial node.