Inhibitors of GlyT1 and GlyT2 differentially modulate inhibitory transmission

@article{Xu2005InhibitorsOG,
  title={Inhibitors of GlyT1 and GlyT2 differentially modulate inhibitory transmission},
  author={Tai-Xiang Xu and Neng Gong and Tian-Le Xu},
  journal={NeuroReport},
  year={2005},
  volume={16},
  pages={1227-1231}
}
The chronic effects of glycine transporter 1 and 2 inhibitors (sarcosine and ALX-1393, respectively) on miniature inhibitory postsynaptic currents were studied in cultured spinal neurons. We found that sarcosine increased the frequency of overall miniature inhibitory postsynaptic currents without affecting the ratio of glycinergic, mixed and GABAergic miniature inhibitory postsynaptic currents, whereas ALX-1393 changed the ratio by increasing the proportions of GABAergic and mixed miniature… 
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Glycinergic transmission: glycine transporter GlyT2 in neuronal pathologies

Recent advances in understanding the role of GlyT2 in the pathophysiology of inhibitory glycinergic neurotransmission are reviewed, with a focus on the areas of caudal areas of the nervous system and pain transmission.

ALX 1393 inhibits spontaneous network activity by inducing glycinergic tonic currents in the spinal ventral horn

Differential effects of spinally applied glycine transporter inhibitors on nociception in a rat model of neuropathic pain

Spinal Antiallodynia Action of Glycine Transporter Inhibitors in Neuropathic Pain Models in Mice

GlyTs were established as the target molecules for the development of medicaments for neuropathic pain after it was demonstrated that i.v. or intrathecal administration of GlyT1 inhibitors, or knockdown of spinal GlyTs by small interfering RNA of GlyTs mRNA produced a profound antiallodynia effect in a partial peripheral nerve ligation model and other neuropathicPain models in mice.

Glycine and glycine receptor signaling in hippocampal neurons: Diversity, function and regulation

Molecular Basis for Substrate Discrimination by Glycine Transporters*

It is demonstrated that the LeuTAa structure represents a good working model of the Na+/Cl--dependent neurotransmitters and that differences in substrate selectivity can be attributed to a single difference of a glycine residue in transmembrane domain 6 of GLYT1 for a serine residue at the corresponding position ofGLYT2.

Blockade of glycine transporter (GlyT) 2, but not GlyT1, ameliorates dynamic and static mechanical allodynia in mice with herpetic or postherpetic pain.

The results suggest that GlyT2 is a potential target for treatment of dynamic and static allodynia in patients with herpes zoster and postherpetic neuralgia and the lack of efficacy of GlyT1 inhibitor may be explained by activation of NMDA receptors and the down-regulation ofglyT1 in the lumbar dorsal horn.

Glycine transport inhibitors for the treatment of pain.

Glycine receptors support excitatory neurotransmitter release in developing mouse visual cortex

These results define mechanisms that contribute to baseline neurotransmission during critical periods of neuronal development, and help identify synaptic functions that could be impacted by GlyR dysfunction.

Development of an N-Acyl Amino Acid That Selectively Inhibits the Glycine Transporter 2 To Produce Analgesia in a Rat Model of Chronic Pain.

It is demonstrated that 33 provides greater analgesia at lower doses, and does not possess the severe side effects of the very slowly reversible GlyT2 inhibitor, ORG25543 (2).

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