[123I]beta-CIT SPECT imaging of dopamine transporter availability after mazindol administration in human cocaine addicts

Psychopharmacology (Berl). 1998 Jun;137(4):321-5. doi: 10.1007/s002130050625.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / metabolism*
  • Cocaine* / analogs & derivatives*
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Image Processing, Computer-Assisted
  • Iodine Radioisotopes
  • Male
  • Mazindol / pharmacology*
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Neostriatum / metabolism
  • Nerve Tissue Proteins*
  • Substance-Related Disorders / diagnostic imaging
  • Substance-Related Disorders / metabolism*
  • Tomography, Emission-Computed, Single-Photon


  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A3 protein, human
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Mazindol
  • Cocaine