Elinore McCance

Euphorigenic doses of cocaine reduce [123I]β-CIT SPECT measures of dopamine transporter availability in human cocaine addicts

The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [123I]β-CIT ([123I]2β-carbomethoxy-3β-(4-iodophenyl)tropane) binding to striatal dopamine transporters (DAT) was assessed in human cocaine addicts using single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n=6) were injected with [123I]β-CIT and imaged 24 h later under equilibrium conditions. Sequential cocaine infusions (0.28±0.03 and 0.56±0.07 mg/kg) produced significant (P<0.0005) reductions in the specific to non-specific equilibrium partition coefficient, V3″ (6±6 and 17±3%), a measure proportional to DAT binding potential. Regression analysis of the logit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED50) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces behavioral effects in humans at measurable levels of DAT occupancy.

[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.

A Review of Pharmacotherapie for Substance Abuse

New pharmacotherapies have been developed for acute withdrawal and maintenance treatments of alcohol and opioid dependence but not for cocaine dependence. High-dose, long-acting benzodiazepines, beta-blockers, and two antiseizure agents-carbamazepine and valproate-are being used for alcohol withdrawal. For maintenance treatment, opioid antagonists and various serotonergic agents, such as fluoxetine and ondansetron, show promise. For opioid dependence, clonidine-naltrexone detoxification appears quite cost-effective, and buprenorpbine and LAAM (levo-alpha-acetylmethadol) show promise for both detoxification and maintenance. More work is needed, however, to discover an effective agent for target populations of cocaine abusers.