Glycine receptor agonist

Glycine receptor agonists are medications that act as agonists of the glycine receptor. They are compounds that bind to and activate the inhibitory glycine receptor (GlyR), a chloride-permeable ligand-gated ion channel that mediates fast synaptic inhibition primarily in the spinal cord and brainstem.[1] The natural neurotransmitter glycine is considered a full agonist with maximal efficacy, producing an open probability exceeding 95% when the receptor is fully occupied.[2] Partial agonists such as taurine and β-alanine produce submaximal responses compared to glycine, with taurine eliciting approximately half the maximum open probability response.[2] Recent research has identified aminomethanesulfonic acid (AMS) as a potent glycine receptor agonist that is structurally intermediate between glycine and taurine, achieving a maximum single-channel open probability of 0.85 at acidic pH conditions where it remains chemically stable.[2] Contemporary research has focused on developing positive allosteric modulators (PAMs) of glycine receptors as potential therapeutic agents for chronic pain conditions, given that enhanced glycinergic inhibition can provide analgesia.[3] The tricyclic sulfonamide compound AM-1488 has emerged as a prototypical glycine receptor PAM that also exhibits direct agonistic activity, with oral administration at 20 mg/kg reducing allodynia in mouse models of neuropathic pain comparable to pregabalin treatment.[4]

Examples

Agonists

PAMs

See also

References

  1. ↑ Ivica, Nemanja; et_al (16 August 2022). "Aminomethanesulfonic acid illuminates the boundary between full and partial agonists at glycine receptors". eLife. 11 e79148. doi:10.7554/eLife.79148. PMC 9462852. PMID 35975975.
  2. 1 2 3 Ivica, Nemanja; et_al (16 August 2022). "Aminomethanesulfonic acid illuminates the boundary between full and partial agonists at glycine receptors". eLife. 11 e79148. doi:10.7554/eLife.79148. PMC 9462852. PMID 35975975.
  3. ↑ Huang, Xinmin (13 February 2025). "Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide positive allosteric modulator". Scientific Reports. 15: 3028. doi:10.1038/s41598-025-90209-7. PMC 11828983. PMID 39953280. Retrieved 26 August 2025.
  4. ↑ Yévenes, Gonzalo E; Zeilhofer, Hanns Ulrich (7 August 2017). "Glycine receptors and glycine transporters: targets for novel analgesics in the treatment of chronic pain". Pharmacology & Therapeutics. 181 (6): 45–69. doi:10.1016/j.biotechadv.2017.07.011. PMID 28782586.



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