Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia

• DOI: 10.1038/s41386-018-0251-1
• Publication Date: 2018-10-26T18:22:41Z
• Authors: Kimberly E. Vanover; Robert E. Davis; Yun Zhou; Weiguo Ye; James R. Brašić; Lorena Gapasin; Jelena Saillard; Michal Weingart; Robert E. Litman; Sharon Mates; Dean F. Wong
• Keywords: Raclopride; Akathisia; Tolerability

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