Effect of mazindol on extracellular dopamine concentration in human brain measured by PET.

RATIONALE: Mazindol, an appetite suppressant, inhibits the reuptake of dopamine in the synaptic cleft. It has been considered that mazindol might enhance dopamine transmission in the human brain. However, there has been no study that investigated the extracellular dopamine concentration in vivo.

OBJECTIVE: Using positron emission tomography (PET), we aimed to measure the effect of mazindol on the extracellular dopamine concentration and to evaluate how mazindol affects the dopamine system in the healthy human brain.

METHODS: Eleven healthy individuals (six males, five females, age 30.9 ± 4.9 years) were enrolled in this study. Each participant was scanned with [(11)C]raclopride on 1 day without any medicine as baseline condition, and on another day with mazindol as drug condition. In the drug condition, participants took mazindol 0.5 mg (N = 5) or 1.5 mg (N = 6) 2 h before the PET scan. Plasma concentrations of mazindol were measured before the injection of [(11)C]raclopride, and urine concentrations of mazindol were measured after the scan.

RESULTS: After taking mazindol, the calculated decrease in binding potential (ΔBP) in the striatum was 1.74 % for 0.5 mg and 8.14 for 1.5 mg, and the correlation with the blood concentration of mazindol was significant (P = 0.0016, R (2) = 0.69). ΔBP was not significantly correlated with the urine concentration of mazindol (P = 0.84, R (2) = 0.005).

CONCLUSIONS: Mazindol increased the extracellular concentration of dopamine in the human brain, and its effect was dose dependent. A single administration of mazindol, even at usual dosage, elevated dopamine concentration similarly to other addictive drugs, suggesting that the risk of dependence may increase with the mazindol dose.