glycine transporter 1 inhibition

Every compound in the sci-wiki that affects glycine transporter 1 inhibition; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

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←glycine transporter 1 inhibition2/2

Glutamatergic

AMG 747 (Tilapertin)

AMG 747, later given the generic name tilapertin, was Amgen's oral GlyT1 inhibitor entry in the crowded mid-2010s field chasing glycine-mediated NMDA enhancement for schizophrenia's negative symptoms, the same mechanistic lane as bitopertin and Org 25935. Two Phase II trials were run as an add-on to standard antipsychotics in patients with persistent negative symptoms. Pooled results at 12 weeks showed no separation from placebo on the negative-symptom rating scale used. The program's ending was abrupt rather than gradual: one participant on the 40 mg dose developed Stevens-Johnson syndrome/toxic epidermal necrolysis, a rare but life-threatening skin reaction, which triggered early termination of the studies on safety grounds before efficacy conclusions could even be fully drawn out.

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Glutamatergic

Org 25935

Org 25935 was Organon's (later Merck, after the 2009 Schering-Plough/Organon merger) entry into the glycine reuptake inhibitor race, arriving on the scene around the same time as Roche's bitopertin and chasing the identical NMDA-hypofunction rationale for schizophrenia's negative symptoms. It also had a second life as a candidate for relapse prevention in alcohol dependence, based on glycinergic modulation of mesolimbic reward circuitry. The schizophrenia program culminated in the GIANT trial, a 215-patient, multi-center, placebo-controlled study of Org 25935 as an add-on to second-generation antipsychotics in patients with persistent negative symptoms. The drug was well tolerated but did not separate from placebo on negative symptoms or cognition, and Merck did not pursue it further after the 2014 publication, leaving it one of several GlyT1 inhibitors that could not translate the mechanism into a working schizophrenia drug.

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