In vivo pharmacological studies with SK&F 94836, a potent inotrope/vasodilator with a sustained duration of action.
1. SK&F 94836 (racemate) was studied in vivo for its cardiovascular properties in cats and dogs. 2. In anaesthetized cats and dogs SK&F 94836 administered intravenously caused increases in left ventricular contractility and decreases in peripheral vascular resistance at similar doses, thus demonstrating the compound to be a mixed acting positive inotropic/vasodilator agent. 3. In conscious instrumented dogs SK&F 94836 was active via the oral as well as intravenous route. 4. The inodilator activity of SK&F 94836 in conscious and anaesthetized animals occurred in association with minimal changes in either blood pressure or heart rate. 5. Detailed studies carried out on anaesthetized cats indicated that SK&F 94836 caused a balanced dilatation of both resistance and capacitance blood vessels. 6. Haemodynamic studies in anaesthetized cats indicated that as a consequence of the inotropic/vasodilator actions, SK&F 94836 caused significant increases in cardiac output and stroke volume. 7. Detailed studies in anaesthetized dogs indicated that significant inodilator activity occurred in the absence of an increase in myocardial oxygen consumption. 8. The duration of action of SK&F 94836 was sustained following both i.v. and oral administration. 9. We conclude that SK&F 94836, as an orally active inotropic/vasodilator agent with a sustained duration in vivo, has potential utility in the treatment of congestive heart failure.
Gristwood
R W
RW
Department of Pharmacology, Smith Kline & French Research Limited, Welwyn, Hertfordshire.
Comer
M B
MB
Eden
R J
RJ
Taylor
E M
EM
Turner
J A
JA
Wallduck
M
M
Owen
D A
DA
D000758:Anesthesia; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002415:Cats; D004285:Dogs; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D006146:Guanidines; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D014665:Vasodilator Agents; C056215:siguazodan; D010208:Papaverine