In vitro characterization of the adrenoceptor activity of AY-28,925.
The adrenoceptor activity of AY-28,925 (5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]-1 H-indole-7-carboxamide) was evaluated on various isolated vascular and nonvascular tissues. Based upon pA2 values derived from either the antagonism of the effect of isoproterenol on paced guinea pig left atria (pA2 = 7.3), spontaneously beating guinea pig right atria (pA2 = 7.4) or canine saphenous vein (pA2 = 7.3), AY-28,925 demonstrated nonselective beta adrenoceptor antagonist activity. Studies using the spontaneously beating guinea pig right atria and the prostaglandin F2 alpha-contracted canine saphenous vein indicated that AY-28,925 also possessed nonselective beta-adrenoceptor intrinsic efficacy. AY-28,925 was shown to be a selective alpha-1 adrenoceptor antagonist with a pA2 value which was greater against phenylephrine in the rabbit aorta (pA2 = 6.6) than against clonidine in the rat vas deferens (pA2 = 5.4) or B-HT 920 in the canine saphenous vein (pA2 = 5.3). Only in concentrations greater than 2000 times those required for adrenergic activity was AY-28,925 able to inhibit potassium chloride- or prostaglandin F2 alpha-induced contractions of the rabbit aorta. The compound had no significant negative intropic activity. These experiments indicate that AY-28,925 possesses, in decreasing orders of activity: nonselective beta-adrenoceptor properties; a selective alpha-1 adrenoceptor inhibitory effect; and a nonspecific direct relaxing action on vascular smooth muscle.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost; D004285:Dogs; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008433:Mathematics; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011460:Prostaglandins F / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D007211:Indoles; D011460:Prostaglandins F; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C050407:AY 28925; D015237:Dinoprost; D007545:Isoproterenol