Therapeutic applications of drugs acting on alpha-adrenoceptors

For over a decade it has been known that clonidine and alpha-methyldopa lower blood pressure by activating central and peripheral alpha-2-adrenoceptors and prazosin likewise by antagonizing alpha-1-adrenoceptors. During the 1980s, the number of therapeutic indications for drugs which act via these classes of alpha-adrenoceptors has expanded greatly, particularly the non-cardiovascular applications of drugs acting on alpha-2-adrenoceptors. Novel alpha-2-agonists such as detomidine and medetomidine have been introduced into veterinary medicine as sedative/analgesics. It is possible that these and other compounds with better alpha-2-adrenoceptor selectivity than clonidine may be used in human medicine to ease symptoms of anxiety in drug- and alcohol-related withdrawal syndromes, and as preanaesthetic agents. Several novel alpha-2-adrenoceptor antagonists, such as idazoxan and atipamezole, have been developed with improved selectivity compared to the traditional antagonist at these receptors, yohimbine. At present none of these new compounds are registered for use, but several are undergoing clinical trials for a variety of therapeutic applications such as depression (idazoxan), arousal of animals sedated with alpha-2-agonists (atipamezole), and adult-onset diabetes (DG-5128). The established use of yohimbine in the treatment of male sexual impotence has been reconfirmed and several of the above compounds may be evaluated in the future to treat this disorder.