The subclassification of α- and β-adrenoceptors has resulted in many opportunities for drug discovery. Important adrenoceptor targets include β2-agonists as bronchodilators, β1 or β1/β2 antagonists as antihypertensives, centrally acting α2-agonists for a variety of applications and α1-antagonists for hypertension and benign prostatic hyperplasia. The pharmacology and nomenclature of 9 adrenoceptors is now established, with α1, α2 and β-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.
Keywords: Uroselectivity, receptor polymorphism, splice variant, α1L-adrenoceptor, β4-adrenoceptor
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