Distribution and characterization of [3H]mesulergine binding in human brain postmortem

Much interest is currently being directed towards serotonin (5-HT) receptors of type 2C (5-HT_2C) because of their possible involvement in the control of different activities, such as the composition of the cerebrospinal fluid, locomotion, feeding, neuronal excitability and anxiety. The limited information regarding their distribution in the human brain prompted us to investigate, and to characterize the binding of ³H]mesulergine, a HT_2C antagonist, in autopsy samples from 24 subjects.The results showed that the ³H]mesulergine binding represented 95% of the total binding and equilibrium saturation binding experiments resulted in a single straight line, consistent with the presence of one site only. The area with the highest density of ³H]mesulergine binding was the choroid plexus, followed at a significantly lower level by the hippocampus, substantia nigra, basal ganglia, amygdala, hypothalamus and prefrontal cortex. The pharmacological profile of the ³H]mesulergine binding was consistent with that of 5-HT_2C receptors, since the most effective displacers were ritanserin, mesulergine and mianserine, followed by clozapine, ketanserine and m-CPP, while other compounds had a negligible or no effect.These findings, showing a wide distribution of ³H]mesulergine binding sites in the human brain, could provide anatomical bases for the different functions attributable to 5-HT_2C receptors in humans.