Quantitative in vitro and ex vivo autoradiography of the α2-adrenoceptor antagonist [3H]atopamezole

Abstract Atipamezole is an α-adrenoceptor antagonist with high affinity and selectivity for the α 2 -receptor. In vitro autoradiography of [ 3 H]atipamezole on rat and human brain sections revealed a pattern virtually identical to the one observed using 3 H-labeled antagonists such as idazoxan or methoxyidazoxan or agonists such as p-aminoclonidine and 5-bromo-6-(2-imidazolin-2-yl-amino-quinoxaline (UK-14304). In vivo studies of [ 3 H]atipamezole demonstrated good penetration into the brain (0.3–1.8% injected dose/g at 5 min, depending upon brain region). In addition, [ 3 H]atipamezole displayed rapid in vivo clearance of nonspecific binding such that at 1 h following an i.v. injection of the drug (100 μCi/animal, rat tail vein administration) the pattern of radioactivity in the brain correlated very well with the receptor distribution as seen by in vitro autoradiography. Atipamezole binding in vivo was displaceable by idazoxan. These results demonstrate the potential of suitably labeled atipamezole for regional studies of brain α 2 -adrenoceptors in vitro and in vivo, in experimental animals as well as in human positron emission tomography (PET) studies.