Effects of α2‐adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets

Abstract

1 A range of 2–(,5-dihydroimidazolyl)-benzene, -quinoline, and -quinoxaline derivatives and 2-morpholino-4-catechol have been characterized as agonists or partial agonists for human platelet aggregation; and for inhibition of adenylate cyclase by measurement of their effect on platelet [cyclic-3′,5′-AMP]. Antagonist activity for these compounds versus adrenaline as agonist has also been assessed for these two responses. 2 The compounds can be divided into 4 groups. Group I contains compounds that are agonists for both responses; group II, compounds that are agonists for inhibition of adenylate cyclase but antagonists for the aggregatory response; group III, compounds that are agonists for the aggregatory response but are antagonists for inhibition of adenylate cyclase by adrenaline; and group IV, compounds that are antagonists for both responses. 3 In group I the EC₅₀ values for induction of aggregation are not significantly different from the EC₅₀ values for inhibition of adenylate cyclase except for 2-morpholino-4-catechol which is significantly more potent as an inhibitor of adenylate cyclase. 4 In group IV a linear correlation is observed between the K₁ values for the two responses for 8 compounds but 2 other compounds do not conform to this correlation. 5 The data are not consistent with a model in which a single x₂-adrenoceptor mediates both the aggregatory response and inhibition of adenylate cyclase and hence support a model in which unique x₂-adrenoceptors mediate these two responses.