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Chemical compound
Golexanolone
Other names GR-3027; 3α-Ethynyl-3β-hydroxyandrostan-17E -one oxime
(3S ,5S ,8R ,9S ,10S ,13S ,14S ,17E )-3-Ethynyl-17-hydroxyimino-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H -cyclopenta[a ]phenanthren-3-ol
CAS Number
PubChem
CID
ChemSpider
UNII
Formula C 21 H 31 N O 2
Molar mass 329.484 g·mol−1 3D model (
JSmol )
C[C@]12CC[C@](C[C@@H]1CC[C@@H]3[C@@H]2CC[C@]\4([C@H]3CC/C4=N\O)C)(C#C)O
InChI=1S/C21H31NO2/c1-4-21(23)12-11-19(2)14(13-21)5-6-15-16-7-8-18(22-24)20(16,3)10-9-17(15)19/h1,14-17,23-24H,5-13H2,2-3H3/b22-18+/t14-,15-,16-,17-,19-,20-,21-/m0/s1
Key:FFIBGVYTWNPLPN-BZLGYYABSA-N
Golexanolone , also known by the developmental code name GR-3027 , is a
neurosteroid
medication which is under development for the treatment of
hypersomnia and
hepatic encephalopathy .
[1]
[2]
[3]
[4] It acts as a
negative allosteric modulator of the
GABAA receptor .
[1]
[2] The medication selectively antagonizes the stimulatory actions of
inhibitory neurosteroids like
allopregnanolone and
tetrahydrodeoxycorticosterone (THDOC) at the GABAA receptor, while not affecting the activation of the GABAA receptor by
γ-aminobutyric acid (GABA).
[2]
See also
References
^
a
b
"Golexanolone - Umecrine Cognition" . AdisInsight . Springer Nature Switzerland AG.
^
a
b
c Agusti A, Llansola M, Hernández-Rabaza V, Cabrera-Pastor A, Montoliu C, Felipo V (June 2016). "Modulation of GABAA receptors by neurosteroids. A new concept to improve cognitive and motor alterations in hepatic encephalopathy". The Journal of Steroid Biochemistry and Molecular Biology . 160 : 88–93.
doi :
10.1016/j.jsbmb.2015.08.020 .
PMID
26307490 .
S2CID
42040436 .
^ Johansson M, Månsson M, Lins LE, Scharschmidt B, Doverskog M, Bäckström T (May 2018).
"GR3027 reversal of neurosteroid-induced, GABA-A receptor-mediated inhibition of human brain function: an allopregnanolone challenge study" . Psychopharmacology . 235 (5): 1533–1543.
doi :
10.1007/s00213-018-4864-1 .
PMC
5919995 .
PMID
29492615 .
^ Johansson M, Agusti A, Llansola M, Montoliu C, Strömberg J, Malinina E, et al. (September 2015).
"GR3027 antagonizes GABAA receptor-potentiating neurosteroids and restores spatial learning and motor coordination in rats with chronic hyperammonemia and hepatic encephalopathy" . American Journal of Physiology. Gastrointestinal and Liver Physiology . 309 (5): G400-9.
doi :
10.1152/ajpgi.00073.2015 .
PMC
4556948 .
PMID
26138462 .
External links
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see
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α-EMTBL
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Negative modulators:
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3M2B
11-Ketoprogesterone
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α3IA
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GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
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