Dopamine D2 receptor occupancy of lumateperone (ITI-007)

a Positron Emission Tomography Study in patients with schizophrenia

Kimberly E. Vanover, Robert E. Davis, Yun Zhou, Weiguo Ye, James R Brasic, Lorena Gapasin, Jelena Saillard, Michal Weingart, Robert E. Litman, Sharon Mates, Dean Foster Wong

Research output: Contribution to journalArticle

Abstract

Dopamine D2 receptor occupancy (D2RO) is a key feature of all currently approved antipsychotic medications. However, antipsychotic efficacy associated with high D2RO is often limited by side effects such as motor disturbances and hyperprolactinemia. Lumateperone (ITI-007) is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate in development for the treatment of schizophrenia and other disorders. The primary objective of the present study was to determine D2RO at plasma steady state of 60 mg ITI-007, a dose that previously demonstrated antipsychotic efficacy in a controlled trial, administered orally open-label once daily in the morning for two weeks in patients with schizophrenia (N = 10) and after at least a two-week washout period from standard of care antipsychotics. D2RO was determined using positron emission tomography with 11C-raclopride as the radiotracer. Mean peak dorsal striatal D2RO was 39% at 60 mg ITI-007 occurring 1 h post-dose. Lumateperone was well-tolerated with a favorable safety profile in this study. There were no clinically significant changes in vital signs, ECGs, or clinical chemistry laboratory values, including prolactin levels. There were no adverse event reports of akathisia or other extrapyramidal motor side effects; mean scores on motor function scales indicated no motor disturbances with lumateperone treatment. This level of occupancy is lower than most other antipsychotic drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia. If approved, lumateperone may provide a new and safe treatment option for individuals living with schizophrenia.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Jan 1 2018

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Dopamine D2 Receptors
Positron-Emission Tomography
Antipsychotic Agents
Schizophrenia
Hyperprolactinemia
Raclopride
Safety
Corpus Striatum
Psychomotor Agitation
Clinical Chemistry
Vital Signs
Movement Disorders
Standard of Care
Prolactin
Glutamic Acid
Dopamine
Serotonin
Electrocardiography
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Dopamine D2 receptor occupancy of lumateperone (ITI-007) : a Positron Emission Tomography Study in patients with schizophrenia. / Vanover, Kimberly E.; Davis, Robert E.; Zhou, Yun; Ye, Weiguo; Brasic, James R; Gapasin, Lorena; Saillard, Jelena; Weingart, Michal; Litman, Robert E.; Mates, Sharon; Wong, Dean Foster.

In: Neuropsychopharmacology, 01.01.2018.

Research output: Contribution to journalArticle

Vanover, Kimberly E. ; Davis, Robert E. ; Zhou, Yun ; Ye, Weiguo ; Brasic, James R ; Gapasin, Lorena ; Saillard, Jelena ; Weingart, Michal ; Litman, Robert E. ; Mates, Sharon ; Wong, Dean Foster. / Dopamine D2 receptor occupancy of lumateperone (ITI-007) : a Positron Emission Tomography Study in patients with schizophrenia. In: Neuropsychopharmacology. 2018.
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