Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo.
We describe the use of 11CRTI-55 and the Multiple Objects Coincidences Counter (MOCC) to detect in-vivo binding to peripheral serotonin reuptake sites (left chest comprising platelet and lung serotonin reuptake sites) in man. Displacement and preloading experiments with clomipramine and venlafaxine in two healthy volunteers demonstrated that 11CRTI-55 binding is decreased in a dose-dependent fashion by both these drugs which bind to the serotonin transporter. In addition parallel data from the total head curve (representing 11CRTI-55 binding to central serotonin and dopamine (DA) reuptake sites) suggest that prior blockade of the serotonin transporter may be a useful strategy to maximize radioactive counts in the head when measuring the DA transporter. The MOCC is likely to be useful to determine sequential indices of relative serotonin reuptake blockade in patients on treatment.
Malizia
A L
AL
Cyclotron Unit, MRC CRC, Hammersmith Hospital, London, UK. andrea@cu.rpms.ac.uk
Melichar
J M
JM
Brown
D J
DJ
Gunn
R N
RN
Reynolds
A
A
Jones
T
T
Nutt
D J
DJ
D000328:Adult; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002997:Clomipramine / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D003511:Cyclohexanols / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism*; D013909:Thorax / Q000378:metabolism*; D000069470:Venlafaxine Hydrochloride
D002352:Carrier Proteins; D002997:Clomipramine; D003042:Cocaine; D003511:Cyclohexanols; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C493230:SLC6A4 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane