Targeting glycine transporter type 1 (GlyT1) in epilepsy: Pathophysiological rationale and therapeutic perspectives.

Authors

Nikola Gapińska, Michał Abram, Marcin Jakubiec, Anna Rafało-Ulińska, Bernadeta Szewczyk, Krzysztof Kamiński, Piotr Wlaź, Katarzyna Socała

Published in

Pharmacology & therapeutics. Pages 109106. Aug 29, 2026. Epub Aug 29, 2026.

Abstract

Glycine transporter type 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations, thereby maintaining the balance between excitatory and inhibitory neurotransmission in the central nervous system. GlyT1 is expressed predominantly in astrocytes, as well as in neurons, throughout most regions of the mammalian brain, and dysregulation of glycinergic transmission has been implicated in the pathophysiology of several neurological and neuropsychiatric disorders, including schizophrenia, autism spectrum disorder, Parkinson's disease, chronic pain, and epilepsy. Preclinical studies indicate that selective inhibition of GlyT1 can elevate seizure thresholds, modulate hippocampal network activity, and influence epigenetic mechanisms involved in epileptogenesis. In this review, we provide a comprehensive and critical overview of current evidence on GlyT1 as a potential molecular target for antiseizure therapy, highlighting research gaps and future directions. Despite these promising findings, the therapeutic potential of GlyT1 inhibitors remains largely unexplored in chronic and drug-resistant epilepsy models. Moreover, excessive extracellular glycine may overactivate NMDA receptors, posing a risk of adverse effects, including increased seizure susceptibility. Altogether, the preclinical data support the notion that balanced inhibition of GlyT1 may represent a novel mechanistic strategy for the treatment of epilepsy. However, further studies are required to establish its clinical efficacy, optimal dosing, safety profile, and overall therapeutic potential.

PMID:
42668023
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.

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