The anticonvulsant zonisamide positively modulates recombinant and native glycine receptors at clinically relevant concentrations

Devenish, Steven O.; Winters, Bryony L.; Anderson, Lyndsey L.; Arnold, Jonathon C.; McGregor, Iain S.; Vaughan, Christopher W.; Chebib, Mary; Absalom, Nathan L.

doi:10.1016/j.neuropharm.2020.108371

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…Zonisamide is an antiepileptic drug, which has recently been reported to facilitate activation of recombinant and native α1, α2, and α3 GlyRs at therapeutic concentrations [61]. Zonisamide has many potential therapeutic targets including voltage gated Na + channels and T-type Ca 2+ channels and it is unclear which target is responsible for its antiepileptic effect.…”

Section: Other Compounds With Modulatory Actions At Glycine Receptorsmentioning

confidence: 99%

Glycine Receptors in Spinal Nociceptive Control—An Update

Zeilhofer

Werynska

Gingras³

et al. 2021

Biomolecules

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Diminished inhibitory control of spinal nociception is one of the major culprits of chronic pain states. Restoring proper synaptic inhibition is a well-established rational therapeutic approach explored by several pharmaceutical companies. A particular challenge arises from the need for site-specific intervention to avoid deleterious side effects such as sedation, addiction, or impaired motor control, which would arise from wide-range facilitation of inhibition. Specific targeting of glycinergic inhibition, which dominates in the spinal cord and parts of the hindbrain, may help reduce these side effects. Selective targeting of the α3 subtype of glycine receptors (GlyRs), which is highly enriched in the superficial layers of the spinal dorsal horn, a key site of nociceptive processing, may help to further narrow down pharmacological intervention on the nociceptive system and increase tolerability. This review provides an update on the physiological properties and functions of α3 subtype GlyRs and on the present state of related drug discovery programs.

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Section: Other Compounds With Modulatory Actions At Glycine Receptorsmentioning

confidence: 99%

Glycine Receptors in Spinal Nociceptive Control—An Update

Zeilhofer

Werynska

Gingras³

et al. 2021

Biomolecules

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“…Other groups have also identified PAMs of GlyRs that contain sulfonamide moieties, such as zonisamide, which is a therapeutically available anticonvulsant. Zonisamide potentiates GlyRa 1 and, to a lesser extent, GlyRa 3 (Devenish et al, 2021). It potentiates currents elicited by low glycine and taurine concentrations by over 10-fold, likely due to the benzodioxole group interacting with loop B to enhance agonist affinity, similar to AM-3607.…”

Section: F Sulfonamidesmentioning

confidence: 89%

Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies

Gallagher

Harvey

et al. 2022

Pharmacol Rev

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Glycine receptors are ligand-gated ion channels that mediate synaptic inhibition throughout the mammalian spinal cord, brainstem, and higher brain regions. They have recently emerged as promising targets for novel pain therapies due to their ability to produce antinociception by inhibiting nociceptive signals within the dorsal horn of the spinal cord. This has greatly enhanced the interest in developing positive allosteric modulators of glycine receptors. Several pharmaceutical companies and research facilities have attempted to identify new therapeutic leads by conducting large-scale screens of compound libraries, screening new derivatives from natural sources, or synthesizing novel compounds that mimic endogenous compounds with antinociceptive activity.

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Metabolomics Provides Novel Insights into Epilepsy Diagnosis and Treatment: A Review

Lai

Chen

2022

Neurochem Res

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The anticonvulsant zonisamide positively modulates recombinant and native glycine receptors at clinically relevant concentrations

Cited by 3 publications

References 56 publications

Glycine Receptors in Spinal Nociceptive Control—An Update

Glycine Receptors in Spinal Nociceptive Control—An Update

Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies

Metabolomics Provides Novel Insights into Epilepsy Diagnosis and Treatment: A Review

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