Determination of dopamine D2 receptor occupancy by lurasidone using positron emission tomography in healthy male subjects

Dean F. Wong, Hiroto Kuwabara, James Robert Brašić, Thomas Stock, Atul Maini, Emily G. Gean, Antony Loebel

Research output: Contribution to journalArticle

Abstract

Rationale: A positron emission tomography (PET) study of dopamine D 2 receptor occupancy was conducted to support a rational dose selection for clinical efficacy studies with lurasidone, an atypical antipsychotic that was approved for the treatment of schizophrenia by the FDA in late 2010. Objectives: To determine the dopamine D2 receptor occupancy of lurasidone in the ventral striatum, putamen and caudate nucleus, and to characterize the relationship between lurasidone serum concentration and D2 receptor occupancy. Methods: A single oral dose of lurasidone (10, 20, 40, 60, or 80 mg) was administered sequentially to healthy male subjects (n = 4 in each cohort). Two PET scans were performed. For each scan, 20 mCi of [11C]raclopride was administered intravenously as a bolus injection, followed immediately by 90 min of PET scan acquisitions. Results: The D 2 receptor occupancy levels were 41-43 % for 10 mg, 51-55 % for 20 mg, 63-67 % for 40 mg, 77-84 % for 60 mg, and 73-79 % for 80 mg of lurasidone. The relationship between D2 receptor occupancy and the mean serum lurasidone concentration during the PET scan (C PET) was similar for the putamen, caudate nucleus, and ventral striatum regions. Mean D2 receptor occupancy levels correlated well with average peak serum concentration of lurasidone. Conclusions: In healthy volunteers, single doses of lurasidone 40-80 mg resulted in D2 receptor occupancy levels of >60 %, a level of receptor occupancy previously associated with clinical response for atypical antipsychotics.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalPsychopharmacology
Volume229
Issue number2
DOIs
StatePublished - Sep 1 2013

Keywords

  • Antipsychotic agents
  • Dopamine D receptors
  • Dose-response relationship
  • Drug
  • Lurasidone
  • Positron emission tomography

ASJC Scopus subject areas

  • Pharmacology

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