Neurophysiological Effects of Bitopertin in Schizophrenia.

Abstract

PURPOSE/BACKGROUND:

Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist D-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport. This study investigates effects of bitopertin on NMDAR-related event-related potential deficits in schizophrenia.

METHODS/PROCEDURES:

Patients with schizophrenia/schizoaffective disorder were treated with bitopertin (10 mg, n = 29), in a double-blind, parallel group investigation. Auditory mismatch negativity served as primary outcome measures. Secondary measures included clinical symptoms and neurocognitive performance.

FINDINGS/RESULTS:

No significant changes were seen with bitopertin for neurophysiological, clinical, or neurocognitive assessments.

IMPLICATIONS/CONCLUSIONS:

These findings represent the first assessment of the effect of bitopertin on neurophysiological biomarkers. Bitopertin did not significantly affect either symptoms or NMDAR-related biomarkers at the dose tested (10 mg). Mismatch negativity showed high test-retest reliability, supporting its use as a target engagement measure.

• Authors: Joshua T Kantrowitz, Karen A Nolan, Michael L Epstein, Nayla Lehrfeld, Constance Shope, Eva Petkova, Daniel C Javitt
• Journal: Journal of clinical psychopharmacology (J Clin Psychopharmacol) Vol. 37 Issue 4 Pg. 447-451 (Aug 2017) ISSN: 1533-712X [Electronic] United States
• PMID: 28590364 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• (4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
• Glycine Plasma Membrane Transport Proteins
• Piperazines
• Receptors, N-Methyl-D-Aspartate
• SLC6A9 protein, human
• Sulfones

Topics

• Adult
• Double-Blind Method
• Female
• Glycine Plasma Membrane Transport Proteins (antagonists & inhibitors, physiology)
• Humans
• Male
• Middle Aged
• Piperazines (therapeutic use)
• Receptors, N-Methyl-D-Aspartate (physiology)
• Schizophrenia (diagnosis, drug therapy, physiopathology)
• Sulfones (therapeutic use)
• Treatment Outcome