Radioiodinated (-)-2-[4-(3-iodophenyl) piperidino] cyclohexanol: a potential radioligand for mapping presynaptic...

We synthesized the (-)-enantiomer of radioiodinated 2-[4-(3-iodophenyl) piperidino] cyclohexanol ((-)-[125I]-m-iodovesamicol [(-)-[125I]mIV]) and evaluated its in vivo binding specificity and affinity for the vesamicol receptor in the rat brain. Significant amounts (approximately 3% of the injected dose) of (-)-mIV accumulated and retention was prolonged. The accumulation of (-)-[125I]mIV in the brain was significantly reduced by the pre- and post-administration of unlabelled vesamicol (0.5 mumol kg -1). Blocking and displacement studies in vivo showed that the binding affinity of (-)-[125I]mIV for the vesamicol receptor was very high, but that for other receptors was very low. Autoradiographic studies showed that the regional distribution of radioactivity, as revealed by coronal sections of the rat brain, was similar for both (-)-[125I]mIV and (-)-[3H]vesamicol. The results demonstrated that the characteristics of (-)-[125I]mIV for binding sites in rat brain were similar in vivo and in vitro. Radioiodinated (-)-mIV may potentially be useful for studying presynaptic cholinergic neurons in the brain.