Nomenclature and state of the art on alpha1-adrenoceptors

The concept of alpha1-adrenoceptor subtypes was first suggested in the mid 1980s on the basis of the different affinities of certain alpha1-adrenoceptor preparations for the alpha-adrenoceptor agonist, oxymetazoline, and the antagonists, WB4101 and phentolamine. Subsequent characterization of alpha1-adrenoceptors using radioligand binding and functional studies has led to the identification of three native prazosin high-affinity alpha1-adrenoceptor subtypes designated alpha1A, alpha1B and alpha1D, corresponding to the three alpha1-adrenoceptor subtypes (alpha1a, alpha1b and alpha1d) isolated by molecular cloning techniques. Since each of these three subtypes exhibits similar affinity for the selective alpha1-adrenoceptor antagonist, prazosin, [3H]prazosin can be used as a convenient probe to evaluate the interaction of compounds with these adrenoceptor subtypes. Considerable clinical experience over the last few years has provided convincing evidence to support the effectiveness of alpha1-adrenoceptor blockade in the treatment of bladder obstruction due to benign prostatic hyperplasia (BPH). The distribution of alpha1-adrenoceptors in the human prostate tissue has shown that the predominant cloned alpha1-adrenoceptor subtype characterized by RNAase protection assays corresponds to the alpha1a-subtype, formerly classified as alpha1c. Many of the alpha1-antagonists currently prescribed in the treatment of BPH do not exhibit in vitro selectivity between alpha1a-, alpha1b- and alpha1d-subtypes and yet they have good clinical tolerance in terms of low incidence of cardiovascular effects. One possibility to account for these findings is that another alpha1-adrenoceptor subtype could be implicated in human prostatic smooth muscle contraction. A recent report, although confirming the presence of an alpha1a-subtype in human prostate, suggested that an alpha1-adrenoceptor subtype with lower affinity for prazosin, designated alpha1L, which has not been cloned yet, is in fact the predominant alpha1-subtype involved in the contractile response of human prostatic smooth muscle to noradrenaline.