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Chemical compound
Pharmaceutical 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 −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] negative allosteric modulator of the GABAA receptor .[ 1] [ 2] 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]
^ 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 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see here for a full list): α-EMTBL Alcohols (e.g., drinking alcohol , 2M2B )Anabolic steroids Avermectins (e.g., ivermectin )Barbiturates (e.g., phenobarbital )Benzodiazepines (e.g., diazepam )Bromide compounds (e.g., potassium bromide )Carbamates (e.g., meprobamate )Carbamazepine Chloralose Chlormezanone Clomethiazole Dihydroergolines (e.g., ergoloid (dihydroergotoxine) )Etazepine Etifoxine Fenamates (e.g., mefenamic acid )Flavonoids (e.g., apigenin , hispidulin )Fluoxetine Flupirtine Imidazoles (e.g., etomidate )Kava constituents (e.g., kavain )Lanthanum Loreclezole Monastrol Neuroactive steroids (e.g., allopregnanolone , cholesterol , THDOC )Niacin Niacinamide Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil ), cyclopyrrolones (e.g., zopiclone ), imidazopyridines (e.g., zolpidem ), pyrazolopyrimidines (e.g., zaleplon ))Norfluoxetine Petrichloral Phenols (e.g., propofol )Phenytoin Piperidinediones (e.g., glutethimide )Propanidid Pyrazolopyridines (e.g., etazolate )Quinazolinones (e.g., methaqualone )Retigabine (ezogabine) ROD-188 Skullcap constituents (e.g., baicalin )Stiripentol Sulfonylalkanes (e.g., sulfonmethane (sulfonal) )Topiramate Valerian constituents (e.g., valerenic acid )Volatiles /gases (e.g., chloral hydrate , chloroform , diethyl ether , paraldehyde , sevoflurane )Negative modulators: 1,3M1B 3M2B 11-Ketoprogesterone 17-Phenylandrostenol α3IA α5IA (LS-193,268) β-CCB β-CCE β-CCM β-CCP β-EMGBL Anabolic steroids Amiloride Anisatin β-Lactams (e.g., penicillins , cephalosporins , carbapenems )Basmisanil Bemegride Bicyclic phosphates (TBPS , TBPO , IPTBO )BIDN Bilobalide Bupropion CHEB Chlorophenylsilatrane Cicutoxin Cloflubicyne Cyclothiazide DHEA DHEA-S Dieldrin (+)-DMBB DMCM DMPC EBOB Etbicyphat FG-7142 (ZK-31906) Fiproles (e.g., fipronil )Flavonoids (e.g., amentoflavone , oroxylin A )Flumazenil Fluoroquinolones (e.g., ciprofloxacin )Flurothyl Furosemide Golexanolone Iomazenil (123 I) IPTBO Isopregnanolone (sepranolone) L-655,708 Laudanosine Lindane MaxiPost Morphine Morphine-3-glucuronide MRK-016 Naloxone Naltrexone Nicardipine Nonsteroidal antiandrogens (e.g., apalutamide , bicalutamide , enzalutamide , flutamide , nilutamide )Oenanthotoxin Pentylenetetrazol (pentetrazol) Phenylsilatrane Picrotoxin (i.e., picrotin , picrotoxinin and dihydropicrotoxinin )Pregnenolone sulfate Propybicyphat PWZ-029 Radequinil Ro 15-4513 Ro 19-4603 RO4882224 RO4938581 Sarmazenil SCS Suritozole TB-21007 TBOB TBPS TCS-1105 Terbequinil TETS Thujone U-93631 Zinc ZK-93426 GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor
