Subclassification and nomenclature of alpha- and beta-adrenoceptors.

ABSTRACT

The subclassification of alpha- and beta-adrenoceptors has resulted in many opportunities for drug discovery. Important adrenoceptor targets include beta(2)-agonists as bronchodilators, beta(1) or beta(1)/beta(2) antagonists as antihypertensives, centrally acting alpha(2)-agonists for a variety of applications and alpha(1)-antagonists for hypertension and benign prostatic hyperplasia. The pharmacology and nomenclature of 9 adrenoceptors is now established, with alpha(1), alpha(2) and beta-adrenoceptors being divided into three subtypes each. It is unlikely that additional discrete adrenoceptor sequences will be identified; however the presence of "affinity states" can give rise to tissue specific differences in pharmacology for a specific subtype. Polymorphisms and splice variants of adrenoceptors continue to be identified; in some cases these modifications can affect pharmacological characteristics and could influence the efficacy of adrenoceptor-targeted therapy. Selective antagonists are now available of all 9 adrenoceptor subtypes. Although these will not all have therapeutic application, the availability of improved pharmacologic tools could lead to the identification of new adrenoceptor targets.