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

Much interest is currently being directed towards serotonin (5-HT) receptor s of type 2C (5-HT2C) 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 infor mation regarding their distribution in the human brain prompted us to inves tigate, and to characterize the binding of [H-3]mesulergine, a HT2C antagon ist, in autopsy samples from 24 subjects. The results showed that the [H-3] mesulergine binding represented 95% of the total binding and equilibrium sa turation binding experiments resulted in a single straight line, consistent with the presence of one site only. The area with the highest density of [ H-3]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 [H- 3]mesulergine binding was consistent with that of 5-HT2C receptors, since t he most effective displacers were ritanserin, mesulergine and mianserine, f ollowed by clozapine, ketanserine and III-CPP, while other compounds had a negligible or no effect. These findings, showing a wide distribution of [H- 3]mesulergine binding sites in the human brain, could provide anatomical ba ses for the different functions attributable to 5-HT2C receptors in humans. (C) 1999 Elsevier Science BSI. All rights reserved.