[3H]-idazoxan binding to rabbit cerebral cortex recognises multiple imidazoline I2-type receptors: pharmacological characterization and relationship to monoamine oxidase.

1. In rabbit cerebral cortical homogenates, saturation analysis of [3H]-idazoxan, an alpha 2-adrenoceptor antagonist, revealed high affinity binding to a single site with high density. Competition experiments demonstrated that the [3H]-idazoxan recognition site was insensitive to the catecholamines, adrenaline and noradrenaline and possessed a low affinity for the alpha 2- and alpha 1-adrenoceptor antagonists, rauwolscine, yohimbine and prazosin, suggesting that the site was not an adrenoceptor. Mapping [3H]-idazoxan binding sites in the forebrain of rabbits by autoradiography, showed high densities of I2 sites in the medial preoptic area and in the stria terminalis. Moderate binding was found in caudate nucleus, putamen, cerebral cortex and hippocampus. 2. The imidazolines cirazoline, naphazoline, guanabenz and BRL44408 along with amiloride, which is structurally related to the imidazolines, all had high affinity for the [3H]-idazoxan site, suggesting that the site was related to the I2 imidazoline-recognition site described by other groups. However, the imidazolines, clonidine and UK-14,304 and the structurally related rilmenidine all had a low affinity for the binding site, showing that [3H]-idazoxan was not binding to the I1 imidazoline-recognition site found in rat, bovine and human medulla oblongata. 3. Naphazoline, guanabenz, clonidine and amiloride competition studies had Hill slopes which were significantly different from unity (P < 0.01) and computer analysis showed that the [3H]-idazoxan binding data could be best fitted to a model which considers binding to two sites (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)