Bupropion occupancy of the dopamine transporter is low during clinical treatment.
BACKGROUND
Bupropion is thought to treat major depression by blocking the dopamine transporter (DAT) because bupropion appears to have a selective affinity for the DAT. The validity of this mechanism has been questioned because the affinity of bupropion for the DAT is quite low.


OBJECTIVE
To determine the occupancy of bupropion for the DAT during clinical treatment of patients with depression.


METHODS
Positron emission tomography with [(11)C]-RTI32 was used to determine the striatal DAT binding potential (BP) of eight depressed patients before and during treatment with bupropion. BP is proportional to available receptor density (receptors not blocked by drug). Occupancy is the percent change in BP. Eight healthy subjects were similarly studied in a test-retest design.


RESULTS
No significant difference in DAT BP was found after bupropion treatment in comparison to the test-retest data. The occupancy after bupropion treatment was 14% (confidence interval 6-22%) as compared to 7% in the test-retest condition.


CONCLUSIONS
Bupropion treatment occupies less than 22% of DAT sites. This raises the question as to whether a DAT occupancy of less than 22% is therapeutic or whether there is another mechanism involved during treatment with bupropion.
Department of Psychiatry, PET Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada. jmeyer@camhpet.on.ca
Jeffrey H
JH
Meyer
Verdell S
VS
Goulding
Alan A
AA
Wilson
Doug
D
Hussey
Bruce K
BK
Christensen
Sylvain
S
Houle
D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism* / Q000627:therapeutic use*; D016642:Bupropion / Q000378:metabolism* / Q000627:therapeutic use*; D003042:Cocaine / Q000031:analogs & derivatives*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D019275:Radiopharmaceuticals; D014055:Tomography, Emission-Computed
D018687:Antidepressive Agents, Second-Generation; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493214:SLC6A3 protein, human; D016642:Bupropion; C067730:RTI-COC 32; D003042:Cocaine