Modification of the cardiostimulatory and coronary dilator effect of isopreenaline caused by etafenone.
Effect of Etafenone on the Cardisotimulatory (1) In the isolated  guinea-pig heart (Langedorff), 2'-[2-(diethylamino)-ethoxy]-3 -phenyl-propioheonoe  HCI (etafenone, Baxacor) produced a parital and non-competitive inhibition of the stiumulant actions of isoprenaline on glycogen phosphorylase, rate and amplitude of contraction, but did not reduce the increase in coronary flow. (2) In isolated cirular strips from bovine coronary arteries, etafeonoe reduced tension (ED 50 = 2.8 x 10-5M), and increased the relaxing effect of isoprenaline. (3) Etafeonoe inhbitied the acitivty of phosphodiesterase in vitro; the Ki value with the enzyme frombovine coronary arteries was 9.2x10-4M, which was 160-fold higher than the Ki for papaverine.(4) The results suggest that etafenone probably affects the myocardial as well as the coronary smoth muscle cell by a direct inhibitory effect on Caiinflux, which could accountfor the depressant effect and the non-competitive antagonism aginst isoprenaline  in  the heartas well as the relaxing action on coronary smooth  muscle. The inhibitory effect on phospodiesterase is likely to contribute to the relaxing action of etafenone by accumulation ofcyclic AMP.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology; D004048:Diethylamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors; D006005:Phosphorylases / Q000037:antagonists & inhibitors; D011427:Propiophenones / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D004048:Diethylamines; D010726:Phosphodiesterase Inhibitors; D011427:Propiophenones; D006005:Phosphorylases; D007545:Isoproterenol