BINDING OF NEW CIRAZOLINE DERIVATIVE TO IMIDAZOLINE RECEPTORS FROM HUMAN BRAIN

Imidazoline compounds are known to interact with alpha(2)-adrenoceptor s as well as with specific non-adrenergic binding sites. Such binding sites are present in the brain and in peripheral tissues. Hypotensive effects of imidazolines were shown To be related to specific interacti on with imidazoline binding sites within the brainstem. Heterogeneity of these sites based on differences in selectivities was reported. In order to facilitate the characterization of human brain imidazoline re ceptors, we synthetized new ligands by substitutions on the cirazoline phenyl ring. Affinities of these cirazoline derivatives were determin ed in two imidazoline binding site models, namely the human brain and the rabbit kidney. Interaction of these compounds with imidazoline bin ding sites from the human brain appeared more sensitive to structural variations of the imidazoline than those with rabbit kidney sites. Mor eover, no correlation was found between affinities for imidazoline bin ding sites and those for alpha(2)-adrenoceptors of the rat brain. Aryl azide derivative of 2-(5-amino-2-methyl-phenoxymethyl)-imidazoline exh ibited a higher affinity for human brain imidazoline binding sites tha n for human brain alpha(2)-adrenoceptors. Photoincorporation of this a zido-compound in human brain imidazoline binding sites was achieved an d blockade of [H-3]idazoxan imidazoline specific binding observed. The se new tools may allow fine characterization of the different subtypes of imidazoline binding proteins. Copyright (C) 1996 Elsevier Science Ltd.