Distribution and pharmacology of alpha 2-adrenoceptors in the central nervous system

E MacDonald, M Scheinin - Journal of Physiology and …, 1995 - agro.icm.edu.pl
E MacDonald, M Scheinin
Journal of Physiology and Pharmacology, 1995agro.icm.edu.pl
Three subtypes of the o,-adrenoceptor have been characterized. The drugs currently
available which most specifically activate (eg dexmedetomidine) or antagonize x,-receptors
(eg atipamezole, idazoxan) do not show significant differences in their affinities for the
subtypes. The drugs which do-show some subtype selectivity (oxymetazoline for o,,;
prazosin for o, and o,) are not useful for in vivo pharmacology due to their relative
nonspecificity in binding to other receptors (eg o,-adrenoceptors). By examining the …
Three subtypes of the o,-adrenoceptor have been characterized. The drugs currently available which most specifically activate (eg dexmedetomidine) or antagonize x,-receptors (eg atipamezole, idazoxan) do not show significant differences in their affinities for the subtypes. The drugs which do-show some subtype selectivity (oxymetazoline for o,,; prazosin for o, and o,) are not useful for in vivo pharmacology due to their relative nonspecificity in binding to other receptors (eg o,-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 o, 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 o, receptors was only found in thalamus. The o, 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 o,-agonists and antagonists.
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