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.

中文翻译：

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多巴胺D2受体对Lumateperone的占有率（ITI-007）：精神分裂症患者的正电子发射断层扫描研究。

多巴胺D2受体占有率（D2RO）是所有当前批准的抗精神病药物的关键特征。但是，与高D2RO相关的抗精神病功效通常受到诸如运动障碍和高泌乳素血症等副作用的限制。Lumateperone（ITI-007）是开发用于治疗精神分裂症和其他疾病的5-羟色胺，多巴胺和谷氨酸的一流选择性同时同步调节剂。本研究的主要目的是确定血浆稳定状态为60 mg ITI-007的D2RO，该剂量以前在对照试验中显示出抗精神病药的功效，该药物每天早晨口服一次，连续两周于患有糖尿病的患者中进行精神分裂症（N = 10），并且经过至少2周的抗精神病药物标准治疗后才消失。D2RO使用正电子发射断层扫描（11C-雷氯必利）作为放射性示踪剂测定。在给药后1小时出现60 mg ITI-007时，平均背侧纹状体D2RO峰值为39％。在这项研究中，Lumateperone具有良好的耐受性，并具有良好的安全性。生命体征，ECG或临床化学实验室值（包括催乳素水平）没有临床上的显着变化。没有关于静坐症或其他锥体束外运动副作用的不良事件报告；运动功能量表的平均评分表明，使用Lumateperone治疗不会引起运动障碍。在其有效剂量下，这种水平的占用低于大多数其他抗精神病药物，并且可能有助于提高黄体酮的安全性和耐受性，并降低运动障碍和高泌乳素血症的风险。如果获得批准，