A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies

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• 作者：Zhizhen Zeng ; Julie A. O'Brien ; Wei Lemaire ; Stacey S. O'Malley ; Patricia J. Miller ; Zhijian Zhao ; Michael A. Wallace ; Conrad Raab ; Craig W. Lindsley ; Cyrille Sur ; David L. Williams Jr.
• 关键词：Glycine ; GlyT1 ; Schizophrenia ; Autoradiography
• 刊名：Nuclear Medicine and Biology
• 出版年：2008
• 出版时间：April 2008
• 年：2008
• 卷：35
• 期：3
• 页码：315-325
• 全文大小：953 K

文摘

In an effort to develop agents to test the NMDA hypofunction hypothesis of schizophrenia, benchmark compounds from a program to discover potent, selective, competitive glycine transporter 1 (GlyT1) inhibitors were radiolabeled in order to further study the detailed pharmacology of these inhibitors and the distribution of GlyT1 in brain. We here report the in vitro characterization of [³⁵S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl)benzamide ([³⁵S]ACPPB), a radiotracer developed from a potent and selective non-sarcosine-derived GlyT1 inhibitor, its use in autoradiographic studies to localize (S)-2-amino-6-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl)benzamide (ACPPB) binding sites in rat and rhesus brain and for in vivo occupancy assays of competitive GlyT1 inhibitors.