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

Abstract

The in vivo potency of mazindol for binding to striatal dopamine transporters (DAT) was assessed by [¹²³I]β-CIT ([¹²³I]2β-carbomethoxy-3β-(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 2mg/day and 4mg/day mazindol. For each scan, subjects were injected with [¹²³I]β-CIT and imaged 24h 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., 2–4mg) occupy a small percentage (i.e., <25%) of DAT in human cocaine abusers and that much higher, potentially intolerable doses (i.e., ≥30mg/day) may be required to antagonize significantly cocaine binding in vivo.