Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol.

Rationale: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated.
Objectives: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol.
Methods: Ten healthy male volunteers were orally administered a placebo and a clinical dose of mazindol (1.5 mg) on separate days. The psychological effects of mazindol were assessed using a visual analogue scale to detect alterations in the state of consciousness. The amount of blockade of dopamine transporters was assessed using positron emission tomography with [ ¹⁸ F]FE-PE2I and extracellular dopamine release was measured as the amount of change in [ ¹¹ C]raclopride binding.
Results: Following administration of a clinical dose of mazindol, the dopamine transporters were blocked by 24-25 %, and the binding potential of [ ¹¹ C]raclopride was reduced by 2.8-4.6 %. The differences of a score measuring derealisation and depersonalization associated with a positive basic mood were significantly correlated with the change in the [ ¹¹ C]raclopride binding in the limbic striatum.
Conclusions: A subtle alteration in the state of consciousness was detected with a correlation to the changes in the [ ¹¹ C]raclopride binding, which implies that a subtle alteration in extracellular dopamine concentration in the limbic striatum by a small amount of dopamine transporter occupancy can affect the state of consciousness. TRIAL REGISTRATION HTTPS://UPLOAD.UMIN.AC.JP/CGI-OPEN-BIN/CTR_E/CTR_VIEW.CGI?RECPTNO=R000009703 : UMIN000008232.