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 name GRX-917) is a deuterated drug which is under development for the treatment of anxiety disorders and mood disorders.[1][2][3][4][5]

Drug development

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

Chemistry

Deuterated etifoxine is a deuterated form of etifoxine (Stresam) with improved pharmacokinetic properties, for instance a longer elimination half-life and duration of action.[1][3][5] Etifoxine has been widely used as an anxiolytic for many decades.[6][7][8][3]

Biology

Etifoxine and deuterated etifoxine are GABAA receptor positive allosteric modulators (GABAkines) and ligands of the translocator protein (TSPO), both of which may contribute to anxiolytic effects.[6][8][2][7] The TSPO promotes steroidogenesis of inhibitory neurosteroids such as allopregnanolone, which act as potent 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 in phase 1 clinical trials for anxiety disorders and preclinical development for mood disorders.[1]

See also

References

  1. ^ a b c d "Etifoxine deuterated - GABA Therapeutics - AdisInsight".
  2. ^ a b c Rupprecht 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. ^ a b c d Rupprecht 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. ^ a b Witkin 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. ^ a b Golani 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. ^ a b Sartori 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. ^ a b Nuss 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. ^ a b Poisbeau 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.

External links



GABAA receptor positive modulators
Translocator protein modulators
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