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.
Baumann
M H
MH
Clinical Psychopharmacology Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Mash
D C
DC
Staley
J K
JK
D000328:Adult; D001665:Binding Sites; D001667:Binding, Competitive; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005277:Fenfluramine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000378:metabolism*
D015306:Biogenic Monoamines; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D005277:Fenfluramine; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine; D004298:Dopamine; D009638:Norepinephrine