Research Imaging Centre, CAMH, Toronto, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada.
Br J Pharmacol. 2020 Aug;177(15):3464-3472. doi: 10.1111/bph.15067. Epub 2020 May 23.
BF2.649 (pitolisant, Wakix®) is a novel histamine H receptor inverse agonist/antagonist recently approved for the treatment of narcolepsy disorder. The objective of the study was to investigate in vivo occupancy of H receptors by BF2.649 using PET brain imaging with the H receptor antagonist radioligand [ C]GSK189254.
Six healthy adult participants were scanned with [ C]GSK189254. Participants underwent a total of two PET scans on separate days, 3 h after oral administration of placebo or after pitolisant hydrochloride (40 mg). [ C]GSK189254 regional total distribution volumes were estimated in nine brain regions of interest with the two tissue-compartment model with arterial input function using a common V across the regions. Brain receptor occupancies were calculated with the Lassen plot.
Pitolisant, at the dose administered, provided high (84 ± 7%; mean ± SD) occupancy of H receptors. The drug was well-tolerated, and participants experienced few adverse events.
The administration of pitolisant (40 mg) produces a high occupancy of H receptors and may be a new tool for the treatment of a variety of CNS disorders that are associated with mechanisms involving H receptors.
BF2.649（pitolisant，Wakix®）是一种新型组胺 H 受体反向激动剂/拮抗剂，最近被批准用于治疗嗜睡症。本研究的目的是使用 H 受体拮抗剂放射性配体[ C]GSK189254 通过 PET 脑成像研究 BF2.649 在体内对 H 受体的占有率。
6 名健康成年参与者接受了[ C]GSK189254 的扫描。参与者在单独的两天内进行了总共两次 PET 扫描，分别在口服安慰剂或盐酸匹多莫德（40mg）后 3 小时进行。使用具有动脉输入功能的两个组织区室模型，通过在整个区域使用共同的 V，在 9 个感兴趣的脑区估算[ C]GSK189254 区域总分布容积。使用 Lassen 图计算脑受体占有率。
在给予的剂量下，匹多莫德提供了高（84±7%；平均值±标准差）的 H 受体占有率。该药物耐受性良好，参与者仅经历了少数不良反应。
匹多莫德（40mg）的给药可产生高的 H 受体占有率，可能成为治疗与 H 受体相关机制相关的各种中枢神经系统疾病的新工具。
