Pharmacological characterization of I1 and I2 imidazoline receptors in human striatum.

ABSTRACT

[3H]RX821002, [3H]clonidine and [3H]idazoxan have previously been shown to selectively label alpha 2-adrenergic receptors, I1 and I2 imidazoline 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, cirazoline and RX801077 display imidazoline receptor selectivity. Our results indicate that for all molecules tested, idazoxan and 'flat' analogs possess I1/I2 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 difference in IC50 between both imidazoline receptors. Both receptors also display similar stereoselectivity, suggesting that they might be 'interconnected' in the human striatum.