Physics:Deuterated etifoxine
| Clinical data | |
|---|---|
| Other names | Etifoxine deuterated; GRX-917 |
| Routes of administration | Oral administration |
| Drug class | GABAA 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
- ↑ 1.0 1.1 1.2 1.3 "Etifoxine deuterated - GABA Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800056063.
- ↑ 2.0 2.1 2.2 "Translocator protein (18kDa) TSPO: a new diagnostic or therapeutic target for stress-related disorders?". Mol Psychiatry 27 (7): 2918–2926. July 2022. doi:10.1038/s41380-022-01561-3. PMID 35444254. https://epub.uni-regensburg.de/52300/1/s41380-022-01561-3.pdf.
- ↑ 3.0 3.1 3.2 3.3 "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. doi:10.1007/s00406-022-01532-3. PMID 36574032.
- ↑ 4.0 4.1 "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. doi:10.1016/j.pbb.2021.173321. PMID 35041859.
- ↑ 5.0 5.1 "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. doi:10.1002/bdd.2313. PMID 35194800.
- ↑ 6.0 6.1 "Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders". Pharmacol Ther 204: 107402. December 2019. doi:10.1016/j.pharmthera.2019.107402. PMID 31470029.
- ↑ 7.0 7.1 "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. doi:10.2147/NDT.S200568. PMID 31308671.
- ↑ 8.0 8.1 "Anxiolytics targeting GABAA receptors: Insights on etifoxine". World J Biol Psychiatry 19 (sup1): S36–S45. 2018. doi:10.1080/15622975.2018.1468030. PMID 30204559.
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