Clinical overview of the novel inotropic agent toborinone.
Toborinone (OPC-18790, Otsuka Pharmaceutical Co. Ltd, 2(1H) -quinolone,6-[3-[ [3,4-dimethoxyphenyl)methyl] amino]-2-hydroxy prop oxyl]-,(.+-.)-) is a novel iv. inotropic agent. Positive inotropic effects are produced by PDE inhibition with the resulting increase in cAMP and intracellular calcium levels. Unlike other inotropic agents that increase cAMP, there is an absence of positive chronotropic effects, which are attributed to prolongation of the action potential due to blockade of delayed rectifier currents. There is also marked venous and arterial vasodilating properties. The absence of heart rate increases results in decreased myocardial oxygen consumption compared with conventional inotropes. Studies in human heart failure patients have been consistent with previous work in animal studies, confirming the effects of toborinone as being positive inotropy (relatively weak), marked arterial and venous vasodilatation and absence of increase in myocardial oxygen consumption. Data regarding safety in larger clinical trials, particularly regarding arrhythmias, is at present unavailable. This information will determine whether this agent becomes an accepted iv. therapeutic option for congestive heart failure.
MacGowan
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Cardiovascular Institute of the University of Pittsburgh Medical Center, S550 Scaife Hall, 200 Lothrop St., Pittsburgh, PA 15213, USA. macgowanga@msx.upmc.edu
D000818:Animals; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D015363:Quinolones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D015363:Quinolones; C077543:toborinone