EFAROXAN (RX-821037) IS A POTENT AND SELECTIVE ALPHA-2-ADRENOCEPTOR ANTAGONIST IN HUMAN FRONTAL-CORTEX MEMBRANES

The antagonist [H-3]idazoxan binds with comparable affinity to alpha-2 adrenergic receptors and to non-adrenergic "idazoxan sites" in human frontal cortex membranes (K(D) = 23 and 28 nM). RX 811033, the 2-ethyl derivative of idazoxan, displays about equal affinity for the alpha-2 receptors as idazoxan but much lower affinity for the idazoxan sites (K(i) = 19 nM and 28-mu-M). Compared to RX 811033, efaroxan (RX 821037) has a dihydrobenzylfuranyl ring system instead of a benzodioxan ring. Nevertheless, efaroxan and RX 811033 bind with equal high affinity to the alpha-2 receptors and with equal low affinity to the idazoxan sites. Radioligand binding studies with [H-3]RX 821002, the 2-methoxy derivative of [H-3]idazoxan, confirm that efaroxan is an alpha-2 adrenergic antagonist possessing high affinity for the alpha-2 receptors and high alpha-2 receptor/idazoxan site-selectivity in the human frontal cortex.