Characterization of a new radioiodinated probe for the alpha(2C) adrenoceptor in the mouse brain

[I-125]17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-hydroxyphenethyl)car boxamide or [I-125]rauwolscine-OHPC, a new radioiodinated probe derived fro m rauwolscine was synthesized and its binding characteristics investigated on sections of the mouse caudate putamen. [I-125]rauwolscine-OHPC binding w as saturable and revealed interaction with a single class of binding sites (K-D = 0.171 nM, B-max = 3082 pCi/mg of tissue). The kinetically derived af finity was in close agreement with the affinity evaluated by saturation exp eriments: k(-1)/k(+1) (0.0403 min(-1)/114 10(6) M(-1)min(-1))=0.35 nM. Comp etition studies revealed interaction with one single class of binding sites for each of the twelve compounds tested. The rank of potency suggested an interaction with alpha(2) adrenoceptors (atipamezole greater than or equal to RX 821002 > yohimbine > (-)epinephrine). Moreover, the good affinity of [I-125] rauwolscine-OHPC binding sites for spiroxatrine, yohimbine, WE 4101 , the relatively good affinity for prazosin (K-i=37.4 nM) and the affinity ratio prazosin/oxymetazoline (37.4/43.4= 0.86) were consistent with an alph a(2C) selective labelling of [I-125]rauwolscine-OHPC. The distribution of [ I-125]rauwolscine-OHPC binding sites in mouse brain was characterized by au toradiography. The density of binding sites was high in the islands of Call eja, accumbens nucleus, caudate putamen and olfactory tubercles, moderate i n the hippocampus, amygdala and anterodorsal nucleus of the thalamus. These findings demonstrated that [I-125]rauwolscine-OHPC is a useful radioiodina ted probe to label alpha(2C) adrenoceptors in mouse brain. (C) 1999 Elsevie r Science Ltd. All rights reserved.