Effects of toborinone (OPC-18790), a new positive inotropic agent, on action potential in guinea pig sinoatrial node: compared with milrinone and E-4031.
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.
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Japan.
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Orito
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Takase
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Fujiki
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Mori
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004594:Electrophysiology; D006168:Guinea Pigs; D008297:Male; D020105:Milrinone; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D011725:Pyridines; D011728:Pyridones; D015363:Quinolones; C063968:E 4031; C077543:toborinone; D020105:Milrinone