ABSTRACT
Compounds interacting with the a-adrenoceptors, such as phenethylamines, imidazolines, and ergot alkaloids, have been used as therapeutic agents for decades. However, many of these drugs also interact with /3-adrenoceptors, or with receptors for other biogenic amines. a-Adrenoceptors were subdivided into the a 1-and aradrenoceptor subtypes approximately 25 years ago [see review by Hieble and Ruffolo (1)]. Based upon radioligand-binding and functional studies, and more recently the application of molecular biological techniques, there appear to exist at least seven subtypes of aadrenoceptors, not including species variants. In concert with the subdivision and subclassification of a-adrenoceptors, there has been a continuing effort to design agonists and antagonists that interact selectively with a particular subtype, in an attempt to apply this subtype selectivity to the design of safer and/or more efficacious drugs. Although agents showing a variety of selectivity profiles have been identified, highly selective agonists or antagonists for most of the adrenoceptor subtypes are not yet available.
