Profile of cardiac and coronary vasodilator effects of MS-857, a novel cardiotonic agent, assessed in isolated, blood-perfused heart preparations of the dog.
MS-857 is a novel orally active nonglycoside and nonsympathomimetic cardiotonic agent. Cardiovascular properties of MS-857 were assessed in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparation of the dogs. MS-857 (0.3-100 nmol) was injected intraarterially (i.a.). In paced papillary muscles, the drug produced a dose-dependent increase in developed tension. In spontaneously beating papillary muscles, MS-857 was ineffective on the ventricular automaticity. The drug increased sinus rate in SA node preparations and shortened AV conduction time by accelerating AV nodal conduction in AV node preparations. In all preparations, MS-857 increased coronary blood flow. The drug produced no arrhythmia in all doses tested. At doses which MS-857 produced a 50% increase in developed tension of papillary muscle, the drug also produces coronary vasodilatation with minimal chronotropic and dromotropic effects. In having such a cardiovascular profile, MS-857 resembles both milrinone and MCI-154 among few cardiotonic agents.
Maruyama
M
M
Institute of Biological Science, Mitsui Pharmaceuticals, Mobara, Chiba, Japan.
Kamiya
J
J
Kobari
T
T
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D012849:Sinoatrial Node / Q000187:drug effects; D044005:Tetrahydroisoquinolines; D014664:Vasodilation / Q000187:drug effects*
D002316:Cardiotonic Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C059136:MS 857