The dopamine stabilizer (-)-OSU6162 occupies a subpopulation of striatal dopamine D2/D3 receptors: an [(11)C]raclopride PET study in healthy human subjects

Neuropsychopharmacology. 2015 Jan;40(2):472-9. doi: 10.1038/npp.2014.195. Epub 2014 Aug 5.


(-)-OSU6162 is a dopamine stabilizer that can counteract both hyperdopaminergic and hypodopaminergic states. In this study, D2/D3 receptor occupancy of (-)-OSU6162 in the human brain was investigated using positron emission tomography (PET). Twelve male healthy volunteers underwent [(11)C]raclopride PET scanning before and 1 h after a single oral dose of (-)-OSU6162 (15-90 mg). Blood samples for determination of (-)-OSU6162 and prolactin plasma levels were collected at Tmax. Parametric images of [(11)C]raclopride binding potential relative to nondisplaceable tissue (cerebellar grey matter) uptake (BPND) at baseline and after (-)-OSU6162 administration were generated using the simplified reference tissue model. MRI-based regions of interest were defined for the striatum, composed of caudate nucleus and putamen, and projected onto the co-registered parametric [(11)C]raclopride BPND image. Furthermore, three striatal subregions, ie, anterior dorsal caudate, anterior dorsal putamen, and ventral striatum, were defined manually and additionally analyzed. Plasma concentrations of (-)-OSU6162, ranging from 0.01 to 0.9 μM, showed a linear relationship with prolactin levels, reflecting blockade of pituitary D2 receptors. A concentration-dependent increase in striatal D2/D3 receptor occupancy was observed, reaching a value of about 20% at an (-)-OSU6162 plasma level of 0.2 μM, and which for higher concentrations leveled off to a maximal occupancy of about 40%. Findings were similar in the striatal subregions. The present data corroborate the notion that (-)-OSU6162 binds preferentially to a subpopulation of D2/D3 receptors, possibly predominantly extrasynaptic, and this may form the basis for the dopamine-stabilizing properties of (-)-OSU6162.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Carbon Radioisotopes
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Dopamine Agents / blood
  • Dopamine Agents / pharmacology*
  • Humans
  • Image Processing, Computer-Assisted
  • Linear Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Piperidines / blood
  • Piperidines / pharmacology*
  • Positron-Emission Tomography
  • Prolactin / blood
  • Raclopride
  • Radiopharmaceuticals
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*


  • Carbon Radioisotopes
  • Dopamine Agents
  • Piperidines
  • Radiopharmaceuticals
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • OSU 6162
  • Raclopride
  • Prolactin