rel-N-Methyl-N-[[(1R,2S)-1,2,3,4-tetrahydro-6-methoxy-1-phenyl-2-naphthalenyl]methyl]glycine hydrochloride

Enzyme inhibitor

This synthetic drug (FW = 339.43 g/mol; CAS 949588-40-3), known systematically as 2-([(1R,2S)-6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen- 2-yl]methylmethylamino)acetate, is a selective inhibitor of the sodium/chloride-dependent glycine transporter GlyT1, counteracting the effects of the dissociative drug ketamine. Rationale: Elevation of extracellular synaptic concentration of glycine by blockade of GlyT1 is believed to potentiate NMDA receptor function in vivo, thereby suggesting a rational approach for the treatment of schizophrenia and cognitive disorders. Moreover, accumbal glycine receptors (GlyRs) are involved in mediating the dopamine activating effects of ethanol, and that administration of glycine locally into the nucleus accumbens (nAc) reduces ethanol consumption in ethanol high-preferring rats. Org-25935 decreased ethanol intake and ethanol preference, as compared with vehicle, whereas water intake was unaffected. This effect was dose-dependent, developed gradually and was sustained for up to 40 days Note: Other GlyT1 inhibitors include GSK931145, Lu AA21279, NFPS, Org 25935, SB-710622, SSR 504734, whereas D-serine is an agonist. All GlyT1 inhibitors increased seizure thresholds dose-dependently, indicative of anticonvulsant activity.