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- W58903049 endingPage "99" @default.
- W58903049 startingPage "51" @default.
- W58903049 abstract "The treatment of schizophrenia has long been dominated by aminergic receptor antagonist-based therapeutics largely founded on the dopamine hypothesis of schizophrenia. More recently the glutamatergic theory has come to the fore which may potentially address some of the deficiencies of current therapies. While there are many approaches to manipulating the glutamatergic system, the most advanced approach is to increase synaptic concentrations of the NMDA receptor co-agonist glycine via inhibition of the glycine transporter 1 (GlyT-1). Here we will describe the background biological rationale for this approach and review the diverse classes of compounds which have been identified as GlyT-1 inhibitors with particular focus on the identification of those molecules which have entered the clinical stages of development. The role of target kinetics in drug action, a review of the rich vein of PET ligand development and their use in clinical development and the status of clinical-stage compounds will be addressed. Finally there is a discussion of some of the issues that have arisen with the discovery and development of GlyT-1 inhibitors and the prospects for the future of this mechanistic approach." @default.
- W58903049 created "2016-06-24" @default.
- W58903049 creator A5022208988 @default.
- W58903049 creator A5028411455 @default.
- W58903049 date "2014-01-01" @default.
- W58903049 modified "2023-09-25" @default.
- W58903049 title "GlyT-1 Inhibitors: From Hits to Clinical Candidates" @default.
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