Abstract

Sgd 101/75 [2-(2-methylindazol-4-imino)-imidazolidine hydrochloride] is an alpha 1 adrenoceptor agonist that shows a greater sensitivity to receptor alkylation with phenoxybenzamine (POB) than norepinephrine (NE) (present study). J. Coates, D.G. Weetman and their co-workers have concluded that Sgd 101/75 is selective for a subtype of alpha-1 receptors, i.e., alpha-1s. The present studies have shown that Sgd 101/75 was a full agonist in the rat anococcygeus muscle and acts at alpha-1 adrenoceptors, as determined by Schild analysis of prazosin antagonism (pKB = 9.24 +/- 0.21, slope = 0.87 +/- 0.13). Alkylation experiments showed that the contractile effects of Sgd 101/75 were more sensitive to POB than the effects of NE. These experiments also allowed the determination of KA values for these agonists (Sgd 101/75 KA = 1.5 +/- 0.6 X 10(-5) M, NE KA = 2.6 +/- 1.0 X 10(-6) M). At 3 X 10(-8) M POB (10 min), the contractile effect of Sgd 101/75 was eliminated, whereas the concentration-effect curve for NE was shifted approximately one log unit to the right with a 20% decrease in maximal response. After similar POB treatment, incubation with Sgd 101/75 (60 min, 3 X 10(-6) to 3 X 10(-4) M) shifted the NE curve to the right in a concentration-dependent manner. Schild regression of these data yielded a pKB = 5.22 +/- 0.09 and slope = 0.87 +/- 0.08. This pKB (-log KB) showed that Sgd 101/75 was competing for the same receptor after POB treatment and before POB treatment (mean of -log KA = 4.92 +/- 0.12).(ABSTRACT TRUNCATED AT 250 WORDS)