Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia

J Clin Psychopharmacol. 2013 Apr;33(2):162-9. doi: 10.1097/JCP.0b013e3182825bce.

Abstract

Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / metabolism*
  • Antipsychotic Agents / pharmacokinetics
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Case-Control Studies
  • Corpus Striatum / metabolism
  • Dopamine Antagonists / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / metabolism*
  • Piperazines / pharmacokinetics
  • Piperidines / administration & dosage
  • Piperidines / metabolism*
  • Piperidines / pharmacokinetics
  • Positron-Emission Tomography / methods
  • Pyrrolidines / metabolism
  • Raclopride / metabolism
  • Receptors, Dopamine D2 / metabolism*
  • Salicylamides / metabolism
  • Schizophrenia / drug therapy*
  • Tissue Distribution
  • Young Adult

Substances

  • Antipsychotic Agents
  • Dopamine Antagonists
  • Piperazines
  • Piperidines
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Salicylamides
  • FLB 457
  • Raclopride
  • blonanserin