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Chemical compound
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
^
a
b
c
d
"Etifoxine deuterated - GABA Therapeutics - AdisInsight" .
^
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 .
^
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 .
^
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 .
^
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 .
^
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 .
^
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 .
^
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 .
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