PHARMACOLOGICAL CHARACTERIZATION OF I-1 AND I-2 IMIDAZOLINE RECEPTORSIN HUMAN STRIATUM

[H-3]RX821002, [H-3]clonidine and [H-3]idazoxan have previously been s hown to selectively label alpha(2)-adrenergic receptors, I-1 and I-2 i midazoline receptors in the human central nervous system, respectively . Idazoxan shows relatively high affinity for all three receptors. We investigated the possible selectivity of several compounds towards one of those receptors in human striatum. Addition of an alkoxy group at the 2-position of the benzodioxan moiety of idazoxan (ethoxy-idazoxan, methoxy-idazoxan) increases the alpha(2)-selectivity in human brain. Efaroxan is also alpha(2)-selective. On the contrary, BU224, BU239, ci razoline and RX801077 display imidazoline receptor selectivity. Our re sults indicate that for all molecules tested, idazoxan and 'flat' anal ogs possess I-1/I-2 receptor selectivity. A 'bulky' substituent at the 2-position of the benzodioxan ring gives rise to alpha(2)-adrenergic receptor selectivity. Until now, we found no more than 3-fold differen ce in IC50 between both imidazoline receptors. Both receptors also dis play similar stereoselectivity, suggesting that they might be 'interco nnected' in the human striatum. Copyright (C) 1996 Elsevier Science Lt d.