A novel positive inotropic series. 2nd communication: in vivo studies of 5- and 6-pyridyl-2(1H)-quinolone derivatives.
In the anaesthetized rabbits and dogs, the 6-pyridyl compounds 14, 32 and 33 (0.1-3 mg/kg) and the 5-pyridyl compounds 6 and 7 (1-10 mg/kg), administered i.v., produced dose-related increases in cardiac contractile force lasting more than 30 min. They also produced relatively minor and shorter-lasting increases in heart rate. Only the 6-pyridyl series decreased blood pressure. The effects were not blocked by propranolol. In the normal haemodynamic states, myocardial oxygen consumption did not increase. When the haemodynamic characteristics of heart failure were produced by propranolol in anaesthetized rabbits and dogs, compounds 14, 32 and 33 reversed these effects, increasing in particular cardiac output. These studies suggest that compounds of the 6-pyridyl series might be beneficial in patients with congestive heart failure.
Decker
N
N
Institut de Pharmacologie, Faculté de Médecine, Strasbourg, France.
Grima
M
M
Velly
J
J
Marciniak
G
G
Leclerc
G
G
Schwartz
J
J
D000758:Anesthesia; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR
D002316:Cardiotonic Agents; D011725:Pyridines; D011804:Quinolines