Autoradiographic studies of RP 62203, a potent 5-HT2 receptor antagonist. Pharmacological characterization of [3H]RP 62203 binding in the rat brain.

The binding properties and localization of [3H]RP 62203, a novel ligand for 5-HT2 receptors, were investigated on rat brain sections. The specific binding of this 5-HT2 receptor antagonist was reversible and could be displaced by ritanserin (1 microM). Saturation experiments revealed a single class of binding sites with a KD of 0.128 +/- 0.018 nM and a Bmax of 1.67 +/- 0.06 pmol/mg protein. Pharmacological specificity was demonstrated by the potency order of displacing agents: RP 62203 > ritanserin > spiperone > methysergide > mianserin > pipamperone > cinanserin > 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Quantitative autoradiography showed a heterogeneous distribution of [3H]RP 62203 binding sites, with the highest densities in the frontal, parietal and auditory cortices (layer IV), claustrum and olfactory bulb. Binding densities in the occipital cortex, caudate putamen and thalamic nuclei were moderate, whereas the hippocampus and substantia nigra displayed a very low density of binding sites. The cerebellar cortex appeared almost devoid of [3H]RP 62203 binding sites. The anatomical distribution of binding sites demonstrated that [3H]RP 62203 essentially bound only to rat brain regions known to contain 5-HT2 receptors. This ligand could thus be a useful tool to visualize 5-HT2 receptors.