Pharmacological prospects for alpha 2-adrenoceptor antagonist therapy

The discovery of various alpha 2-adrenoceptor subtypes in numerous tissues and studies of alpha 2-adrenoceptor-mediated mechanisms has generated considerable interest in their physiological functions. It has also increased possibilities for the design of new pharmacological tools and for the study of the pharmacological impact of new drugs. Alpha 2-adrenoceptors are located pre- and postsynaptically both in the central noradrenergic pathways and on the autonomic nerve endings. It is difficult to dissociate alpha 2-adrenoceptor-mediated autoregulation, involving presynaptic receptors, from actions dependent on post- and extrajunctional alpha 2-adrenoceptor activation. A lot of alpha 2-adrenoceptors are subject to permanent tonic activation by the sympathetic nervous system. Max Lafontan and colleagues review the major actions of alpha 2-adrenoceptors and consider the sites of impact of alpha 2-antagonists that could initiate further research for putative applications of these drugs. Many of the possible targets for alpha 2-adrenoceptor antagonists have not yet been explored clinically.