Pharmacological profile of LAS 31180, a new inotropic/vasodilator quinolone derivative.
LAS 31180 (3-methylsulphonylamino-1-methyl-4(1H)-quinolone, CAS 137338-43-3) was found to have positive inotropic and vasodilator properties through its inhibitory action on type 3 phosphodiesterase. The inotropic effects of LAS 31180 were demonstrated in vitro both in isolated guinea-pig ventricular strips (EC50 of 1.2 mumol/l) and in isolated guinea-pig working hearts. In conscious chronically instrumented Beagle dogs, LAS 31180 administered either by intravenous or oral route, showed a dose-dependent, long-lasting positive inotropic effect with minimal effects on heart rate. In hypertensive Beagle dogs LAS 31180 elicited a potent and long-lasting fall in blood pressure.
Gras
J
J
Department of Pharmacological Development, Almirall Prodesfarma, Research Center, Cardener 68-74, 08024-Barcelona, Spain. jgras@almirallprodesfarma.com
Cardelús
I
I
Beleta
J
J
Gristwood
R W
RW
Palacios
J M
JM
Llenas
J
J
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D013449:Sulfonamides; D014665:Vasodilator Agents; C420205:LAS 31180; D010727:Phosphoric Diester Hydrolases