m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B receptor

The behavioural effects of m-chlorophenylpiperazine (mCPP) in rats and its clinical effects in man are thought to be related to its action at 5-HT2B/2C receptors. However, although mCPP is a partial agonist at these subtypes in rat, its efficacy at human 5-HT2B/2C receptors is unknown. We therefore investigated the activity of mCPP at cloned human 5-HT2B and 5-HT2C receptors. mCPP was a partial agonist at the human 5-HT2C receptor but antagonized the human 5-HT2B receptor. Therefore, while supporting the proposal that at least some of the clinical effects of mCPP are likely to be mediated via stimulation of the 5-HT2C receptor, this study also suggests that any 5-HT2B receptor-mediated effects are more likely to result from receptor blockade than from receptor activation.