DISTRIBUTION AND PHARMACOLOGY OF ALPHA(2)-ADRENOCEPTORS IN THE CENTRAL-NERVOUS-SYSTEM

Three subtypes of the alpha(2)-adrenoceptor have been characterized. The drugs currently available which most specifically activate (e.g. dexmedetomidine) or antagonize alpha(2)-receptors (e.g. atipamezole, idazoxan) do not show significant differences in their affinities for the subtypes, The drugs which do show some subtype selectivity (oxymetazoline for alpha(2A); prazosin for alpha(2B) and alpha(2C)) are not useful for in vivo pharmacology due to their relative nonspecificity in binding to other receptors (e.g. alpha(1)-adrenoceptors). By examining the distribution of the mRNA coding for the three subtypes, it has been possible to map those regions in the brain which possess cells which synthetize the distinct subtypes. The mRNA coding for alpha(2A) receptors is found throughout the brain, especially in locus coeruleus, a region which contains the cell bodies for the ascending and descending noradrenergic neurones. The mRNA for alpha(2B) receptors was only found in thalamus. The alpha(2C) mRNA had a wider distribution, in basal ganglia its expression was particularly Intense. One must hope that the fact that the receptor subtypes are not uniformly distributed throughout the brain means that new subtype selective drugs will not suffer from the same broad diversity of actions of the present alpha(2)-agonists and antagonists.