[123I]beta-CIT SPECT imaging of dopamine transporter availability after mazindol administration in human cocaine addicts.
The in vivo potency of mazindol for binding to striatal dopamine transporters (DAT) was assessed by [123I]beta-CIT ([123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n = 12) underwent three SPECT scans; one before, between, and after subchronic (1 week) administration of 2 mg/day and 4 mg/day mazindol. For each scan, subjects were injected with [123I]beta-CIT and imaged 24 h later under equilibrium conditions. Results showed a statistically significant main effect of mazindol dose (df = 2, F = 10.30, P < 0.001, repeated measures ANOVA) in reducing the specific to non-displaceable equilibrium partition coefficient, V3'' (a measure proportional to DAT binding potential). Regression analysis of the logit transformed data enabled estimation of the 50% displacement dose of mazindol (ED50 = 30mg/day). These data suggest that low doses of mazindol (i.e., 2-4 mg) occupy a small percentage (i.e., < 25%) of DAT in human cocaine abusers and that much higher, potentially intolerable doses (i.e., > or = 30 mg/day) may be required to antagonize significantly cocaine binding in vivo.
Department of Psychiatry, Yale University School of Medicine, Connecticut, USA. robert.malison@yale.edu
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D000328:Adult; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives*; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008297:Male; D008454:Mazindol / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D017072:Neostriatum / Q000378:metabolism; D009419:Nerve Tissue Proteins; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D008454:Mazindol; D003042:Cocaine