The serotonin agonist m-chlorophenylpiperazine (mCPP) binds to serotonin transporter sites in human brain.

The serotonin (5-HT) agonist m-chlorophenylpiperazine (mCPP) is commonly used as a neuroendocrine challenge agent in humans, and it is well accepted that its mechanism of action involves direct stimulation of postsynaptic 5-HT receptors. In the present work, we demonstrate that mCPP also displays appreciable affinity (IC50 = 230 nM) for 5-HT transporters labeled by [125I]3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([125I]RTI-55) in human occipital cortex. These data agree with reports that show mCPP increases extracellular 5-HT in rat brain via a mechanism involving 5-HT transporters. Our results indicate that mCPP may exhibit a presynaptic 5-HT action in man, and studies utilizing mCPP to assess 5-HT receptor sensitivity should be interpreted with caution.