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

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  • Orito Kensuke
    <I>2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.</I>
  • Takase Hiromichi
    <I>2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.</I>
  • Fujiki Hiroyuki
    <I>2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.</I>
  • Mori Toyoki
    <I>2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd.</I>

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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 (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.

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