Demonstration of the beta 2-adrenoceptor intrinsic efficacy of AY-28,925 using the PGF2 alpha-contracted guinea-pig trachea.

The abilities of AY-28,925, labetalol and medroxalol to relax the PGF2 alpha-contracted isolated guinea-pig trachea have been investigated to compare their activities at beta 2-adrenoceptors. Maximum relaxation induced by AY-28,925 was significantly greater than that induced by either labetalol or medroxalol. This relaxation occurred in a concentration-dependent manner over a range of concentrations consistent with the previously determined affinity of AY-28,925 for beta-adrenoceptors. ICI-118,551 inhibited AY-28,925-induced relaxation in a concentration-dependent manner with a pA2 value similar to that determined for ICI-118,551 inhibition of the selective beta 2-adrenoceptor agonist salbutamol, but not the selective beta 1-adrenoceptor agonist norepinephrine. The Schild plot slope for ICI-118,551 inhibition of AY-28,925 or salbutamol did not differ significantly from unity, while that for inhibition of isoproterenol (a non-selective beta-adrenoceptor agonist) did. It is concluded that AY-28,925 is a more efficacious relaxant of tracheal smooth muscle than either labetalol or medroxalol, and that this relaxant activity is the result of its greater intrinsic efficacy at the beta 2-adrenoceptor.