PHARMACOLOGIC AND THERAPEUTIC APPLICATIONS OF ALPHA 2-ADRENOCEPTOR SUBTYPES

There has been a rapid accumulation of new experimental data relating to the pharmacology of !X2-adrenoceptors, including the identification of multiple receptor subtypes and new therapeutic applications for !X2-adrenoceptor agonists and antagonists. In view of the diverse pharmacology of receptors or binding sites defined as "!X2", one must redefine exactly what this designation now includes. For this review, an !X2-adrenoceptor is defined as one that is sensitive to both the physiological catecholamine agonists, norepinephrine and epinephrine, as well as selective agonists, such as B-HT 933 and UK-14,304, and is antagonized by agents such as rauwolscine, yohimbine, and idazoxan. Some !Xz-adrenoceptor subtypes also have a high affinity for prazosin, previously thought to interact only with !Xl-ad­ renoceptors, and others have a relatively low affinity for yohimbine and rauwolscine, compared to other !X2-adrenoceptor antagonists. The three !Xz-adrenoceptor subclassification schemes based on: (a) receptor cloning and expression, (b) correlation of radioligand binding affinity, and (c) antagonist potency in functional assays arc described, as well as discrep­ ancies between the subtypes identified using these schemes. In addition to their long-known efficacy in hypertension, iX2-adrenoceptor agonists are now being utilized clinically for several new indications. The many functions