Deuterated etifoxine explained

Routes Of Administration:Oral administration
Class:GABAA receptor positive allosteric modulator
TSPO ligand
Synonyms:Etifoxine deuterated; GRX-917

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.

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. Etifoxine has been widely used as an anxiolytic for many decades.[6] [7]

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.[8] 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. The precise isotopic substitution of deuterated etifoxine has not yet been disclosed. As of January 2023, deuterated etifoxine is in phase 1 clinical trials for anxiety disorders and preclinical development for mood disorders.

See also

External links

Notes and References

  1. Web site: Etifoxine deuterated - GABA Therapeutics - AdisInsight .
  2. Rupprecht R, Wetzel CH, Dorostkar M, Herms J, Albert NL, Schwarzbach J, Schumacher M, Neumann ID . Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders? . Mol Psychiatry . 27 . 7 . 2918–2926 . July 2022 . 35444254 . 10.1038/s41380-022-01561-3 . 248245591 .
  3. Rupprecht R, Pradhan AK, Kufner M, Brunner LM, Nothdurfter C, Wein S, Schwarzbach J, Puig X, Rupprecht C, Rammes G . 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. December 2022 . 36574032 . 10.1007/s00406-022-01532-3 . 255205221 .
  4. 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 . The imidazodiazepine, KRM-II-81: An example of a newly emerging generation of GABAkines for neurological and psychiatric disorders . Pharmacol Biochem Behav . 213 . 173321 . February 2022 . 35041859 . 10.1016/j.pbb.2021.173321 . 245963990 .
  5. 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 . 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 . April 2022 . 35194800 . 10.1002/bdd.2313 . 247057968 .
  6. Sartori SB, Singewald N . Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders . Pharmacol Ther . 204 . 107402 . December 2019 . 31470029 . 10.1016/j.pharmthera.2019.107402 . free .
  7. Poisbeau P, Gazzo G, Calvel L . Anxiolytics targeting GABAA receptors: Insights on etifoxine . World J Biol Psychiatry . 19 . sup1 . S36–S45 . 2018 . 30204559 . 10.1080/15622975.2018.1468030 . free .
  8. Nuss P, Ferreri F, Bourin M . 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 . 2019 . 31308671 . 6615018 . 10.2147/NDT.S200568 . free .

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