title: Cardiovascular effects of a new positive inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]-ethanol (TA-064) in the anesthetized dog and isolated guinea pig heart.
abstract: The positive inotropic effect of TA-064, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, was studied in the anesthetized dog and isolated guinea pig heart. An intravenous administration of TA-064 dose-dependently increased the cardiac contractile force with little effect on blood pressure in dogs. The positive inotropic activity of TA-064 was 1/100 that of isoproterenol and similar to that of dobutamine. This effect of TA-064 was stereospecific, and it was blocked by practolol. Thus TA-064 has beta 1-adrenoceptor agonistic action. The positive inotropic effect of TA-064 was more pronounced than the positive chronotropic effect, compared with those of isoproterenol. Similar effect of TA-064 was observed in the reserpinized dog and in the isolated perfused heart of the guinea pig as well. TA-064 administered intraduodenally at a dose of 0.1 mg/kg increased contractile force by 120% of the control, and the effect lasted for more than 150 min. TA-064 given in the femoral artery demonstrated a very weak vasodilating effect on the artery. TA-064 is an orally active, positive inotropic agent. The selective positive inotropic action of TA-064 may result from its beta 1-adrenoceptor agonistic property.
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D005269:Femur / Q000098:blood supply; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D004983:Ethanolamines; D010656:Phenylephrine; D004280:Dobutamine; D012110:Reserpine; C037293:denopamine