Glycine uptake inhibitors

Brown A, Carlyle I, Clark J, Hamilton W, Gibson S, et al. 2001. Discovery and SAR of org 24598-a selective glycine uptake inhibitor. Bioorg Med Chem Lett 11 2007-2009. 

Javitt DC, Sershen H, Hashim A, Lajtha A. 1997. Reversal of phencyclidine-induced hyperactivity by glycine and the glycine uptake inhibitor glycyldodecylamide. Neuropsychopharmacology 17 202-204. 

I. Egle etaU US 6,426,364 (July 30, 2002) Assignee NPS Allelix Corp Utility Glycine Uptake Inhibitors... 

Pflra-chloromercunphenylsulfonate is the most potent glycine uptake inhibitor known to date, but imipramine, chlorpromazine, and hydrazinoacetic acid all have some inhibitory action (Aprison et al., 1970). 

GABA uptake inhibitors Kardos et alP Glycine antagonists Salituro et alP... 

SSR-504734 is a potent, selective, and reversible inhibitor (IC50 = 18 nM) that is competitive with glycine [47,51]. The inhibitor rapidly and reversibly blocked the uptake of [14C]glycine in mouse cortical homogenates, which was sustained for up to 7 h. Complete cessation of blockade and return to glycine basal levels occurred prior to 24 h, which is in stark contrast to NFPS (>24 h). SSR-504734 potentiated a nearly twofold increase of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in rat hippocampal slices and produced an increase in contralateral rotations in mice when microinjected into the striatum. Microdialysis experiments indicated that the inhibitor induced a rapid and sustained increase in extracellular glycine levels in the PFC of freely moving rats [51]. The compound also demonstrated efficacy in a variety of psychosis models [51-53]. SSR-504734 was reportedly in clinical trials for schizophrenia but discontinued after Phase I (data not disclosed) [54]. 

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