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Deuterated etifoxine

From Wikipedia, the free encyclopedia
Chemical compound
Pharmaceutical compound
Deuterated etifoxine
Clinical data
Other namesEtifoxine deuterated; GRX-917
Routes of
administration
Oral administration
Drug classGABAA receptor positive allosteric modulator;TSPO ligand

Deuterated etifoxine (developmental code nameGRX-917) is adeuterated drug which is under development for the treatment ofanxiety disorders andmood disorders.[1][2][3][4][5]

Drug development

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It was originated by GABA Therapeutics and is under development by GABA Therapeutics andATAI Life Sciences.[1]

Chemistry

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Deuterated etifoxine is adeuterated form ofetifoxine (Stresam) with improvedpharmacokinetic properties, for instance a longerelimination half-life andduration of action.[1][3][5] Etifoxine has been widely used as an anxiolytic for many decades.[6][7][8][3]

Biology

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Etifoxine and deuterated etifoxine areGABAA receptor positive allosteric modulators (GABAkines) andligands of thetranslocator protein (TSPO), both of which may contribute to anxiolytic effects.[6][8][2][7] The TSPO promotessteroidogenesis ofinhibitoryneurosteroids such asallopregnanolone, which act aspotent GABAA receptor positive allosteric modulators, and hence interactions with the TSPO can also indirectly potentiate the GABAA receptor.[2][3] The precise isotopic substitution of deuterated etifoxine has not yet been disclosed.[4] As of January 2023, deuterated etifoxine is inphase 1clinical trials for anxiety disorders andpreclinical development for mood disorders.[1]

See also

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References

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  1. ^abcd"Etifoxine deuterated - GABA Therapeutics - AdisInsight".
  2. ^abcRupprecht R, Wetzel CH, Dorostkar M, Herms J, Albert NL, Schwarzbach J, Schumacher M, Neumann ID (July 2022)."Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?"(PDF).Mol Psychiatry.27 (7):2918–2926.doi:10.1038/s41380-022-01561-3.PMID 35444254.S2CID 248245591.
  3. ^abcdRupprecht R, Pradhan AK, Kufner M, Brunner LM, Nothdurfter C, Wein S, Schwarzbach J, Puig X, Rupprecht C, Rammes G (December 2022). "Neurosteroids and translocator protein 18 kDa (TSPO) in depression: implications for synaptic plasticity, cognition, and treatment options".Eur Arch Psychiatry Clin Neurosci.273 (7):1477–1487.doi:10.1007/s00406-022-01532-3.PMID 36574032.S2CID 255205221.
  4. ^abWitkin JM, Lippa A, Smith JL, Jin X, Ping X, Biggerstaff A, Kivell BM, Knutson DE, Sharmin D, Pandey KP, Mian MY, Cook JM, Cerne R (February 2022)."The imidazodiazepine, KRM-II-81: An example of a newly emerging generation of GABAkines for neurological and psychiatric disorders".Pharmacol Biochem Behav.213 173321.doi:10.1016/j.pbb.2021.173321.PMID 35041859.S2CID 245963990.
  5. ^abGolani LK, Divović B, Sharmin D, Pandey KP, Mian MY, Cerne R, Zahn NM, Meyer MJ, Tiruveedhula VV, Smith JL, Ping X, Jin X, Lippa A, Schkeryantz JM, Arnold LA, Cook JM, Savić MM, Witkin JM (April 2022). "Metabolism, pharmacokinetics, and anticonvulsant activity of a deuterated analog of the α2/3-selective GABAkine KRM-II-81".Biopharm Drug Dispos.43 (2):66–75.doi:10.1002/bdd.2313.PMID 35194800.S2CID 247057968.
  6. ^abSartori SB, Singewald N (December 2019)."Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders".Pharmacol Ther.204 107402.doi:10.1016/j.pharmthera.2019.107402.PMID 31470029.
  7. ^abNuss P, Ferreri F, Bourin M (2019)."An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action".Neuropsychiatr Dis Treat.15:1781–1795.doi:10.2147/NDT.S200568.PMC 6615018.PMID 31308671.
  8. ^abPoisbeau P, Gazzo G, Calvel L (2018)."Anxiolytics targeting GABAA receptors: Insights on etifoxine".World J Biol Psychiatry.19 (sup1):S36 –S45.doi:10.1080/15622975.2018.1468030.PMID 30204559.

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