piperidines and toborinone

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-b enzoyl) 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 (Vmax) and action potential amplitude (APA). On the other hand, milrinone, a peak III phosphodiesterase (PDE III) inhibitor, increased Vmax and APA and shortened CL and action potential duration. E-4031, an IK blocker, prolonged CL, depolarized MDP and decreased Vmax and APA. These results suggest that toborinone modulates the action potential like an IK blocker rather than a PDE III inhibitor in a sinoatrial node.

Topics: Action Potentials; Analysis of Variance; Animals; Anti-Arrhythmia Agents; Cardiotonic Agents; Electrophysiology; Guinea Pigs; Male; Milrinone; Phosphodiesterase Inhibitors; Piperidines; Pyridines; Pyridones; Quinolones; Sinoatrial Node