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Substitution of the chlorine atom by a radio-iodine in position 5 in the zacopride molecule yielded 125Iiodo-zacopride that bound with high affinity (Kd = 4.3 nM) to 5-HT3 receptors in the rat central nervous system. Assays with membranes from the posterior (mainly entorhinal) cortex confirmed that the pharmacological properties and regional distribution of 125Iiodo-zacopride-specific binding sites were identical with those of 5-HT3 sites labelled by the reference radioligand 3Hzacopride. Autoradiographic investigations for the visualization and quantification of 5-HT3 receptors yielded similar results with both radioligands, but autoradiograms could be obtained after only 1-3 days of exposure of sections labelled with 125Iiodo-zacopride, instead of 4-6 months using 3Hzacopride. The highest density of 5-HT3 sites was found in the nucleus tractus solitarius followed by, in decreasing order, the dorsal motor nucleus of the vagus nerve, the superficial layers of the dorsal horn in the spinal cord, the nucleus of the spinal tract of the trigeminal nerve, and the area postrema. Significant labelling of 5-HT3 receptors was also observed in limbic areas (amygdala, hippocampus, frontal and entorhinal cortex), and to a much lower extent in the dorsal raphe nucleus, striatum, and substantia nigra. These multiple locations further support the idea that 5-HT3 receptors are probably involved in several 5-HT-mediated functions in the central nervous system.
Laporte et al. (Wed,) studied this question.