Glycine is an early and crucial substrate in the biosynthesis of haem; inhibiting its transport by blocking GlyT1 reduces its availability for haem biosynthesis and this reduces the downstream accumulation ofprotoporphyrin IX in people with EPP.[4]
Dysfunction of NMDA receptors may play a key role in the pathogenesis of schizophrenia and modulation ofglutamatergic signalling via increased concentrations of glycine in the synaptic cleft may help potentiate NMDA receptor function and improve the symptoms of schizophrenia.[5]
In aphase II proof-of-concept study, patients on bitopertin experienced a significant improvement in the change of the Negative Symptom Factor Score from baseline within 8 weeks (from −4.86 in the placebo group to −6.65 in the treatment group, p<0.05, per-protocol population). In addition, 83% of patients on bitopertin described an improvement of negative symptoms on the CGI-I1 versus 66% on placebo (p<0.05, per-protocol population).[6]
In January 2014, Roche reported that bitopertin failed to meet its endpoints in twophase III trials assessing its efficacy in reducing negative symptoms of schizophrenia.[2] Subsequently, in April 2014, Roche announced that it was discontinuing all except one of its phase III trials of bitopertin for schizophrenia.[2]
^Umbricht D, Alberati D, Martin-Facklam M, et al. (June 2014). "Effect of bitopertin, a glycine reuptake inhibitor, on negative symptoms of schizophrenia: a randomized, double-blind, proof-of-concept study".JAMA Psychiatry.71 (6):637–46.doi:10.1001/jamapsychiatry.2014.163.PMID24696094.
^Glycine Transporter Type 1 (GLYT1) Inhibitor RG1678: Positive Results of the Proof-of-Concept Study for the Treatment of Negative Symptoms in Schizophrenia, Umbricht D. et al., ACNP 2010
