From Wikipedia, the free encyclopedia
Glufimet Other names RGPU-238; Dimethyl 3-phenylglutamic acid hydrochloride; Dimethyl 3-phenylglutamate hydrochloride; 1,5-Dimethyl (2S )-2-amino-3-phenylpentanedioate hydrochloride
dimethyl 2-amino-3-phenylpentanedioate;hydrochloride
CAS Number PubChem CID ChemSpider CompTox Dashboard (EPA ) Formula C 13 H 18 Cl N O 4 Molar mass 287.74 g/mol g·mol−1 3D model (JSmol )
COC(=O)CC(C1=CC=CC=C1)C(C(=O)OC)N.Cl
InChI=1S/C13H17NO4.ClH/c1-17-11(15)8-10(12(14)13(16)18-2)9-6-4-3-5-7-9;/h3-7,10,12H,8,14H2,1-2H3;1H
Key:YYGZEJCVUMTAMY-UHFFFAOYSA-N
Glufimet (developmental code name RGPU-238 ), also known as dimethyl 3-phenylglutamate hydrochloride , is a derivative of glutamic acid (glutamate) which was developed in Russia and is related to the γ-aminobutyric acid (GABA) derivative phenibut (3-phenyl-GABA).[1] [2] [3] [4] glycine fragments in its chemical structure , has been described as a "GABA precursor ", and is said to modulate the GABA and nitric oxide (NO) systems and to have antioxidant activity.[1] [2] [3] [4] metabotropic glutamate receptors may also play a role in the mechanism of action of glufimet.[4] Stress-protective effects have been described for glufimet in animals.[1] [2] [3]
References
^ a b c Tyurenkov IN, Perfilova VN, Sadikova NV, Berestovitskaya VM, Vasil'eva OS (July 2015). "Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed Animals under Conditions of Nitric Oxide Synthesis Blockade". Bull. Exp. Biol. Med . 159 (3): 384–6. doi :10.1007/s10517-015-2969-7 . PMID 26205724 . ^ a b c Perfilova VN, Popova TA, Prokofiev II, Mokrousov IS, Ostrovskii OV, Tyurenkov IN (June 2017). "Effect of Phenibut and Glufimet, a Novel Glutamic Acid Derivative, on Respiration of Heart and Brain Mitochondria from Animals Exposed to Stress against the Background of Inducible NO-Synthase Blockade". Bull. Exp. Biol. Med . 163 (2): 226–229. doi :10.1007/s10517-017-3772-4 . PMID 28726197 . ^ a b c Perfilova VN, Sadikova NV, Prokofiev II, Inozemtsev OV, Tyurenkov IN (2016). "[Cardioprotective effect of the new derivative of glutamic acid - glufimet in acute immobilization-painful stress in animals of different ages]". Adv Gerontol (in Russian). 29 (1): 116–122. doi :10.1134/S2079057016030073 . PMID 28423256 . ^ a b c Borisov AV, Prokofiev II, Mokrousov IS, Perfilova VN, Tyurenkov IN (December 2017). "Inhibition of the Expression of Inducible NO Synthase by Neuroactive Amino Acid Derivatives Phenibut and Glufimet In Vitro and Ex Vivo". Bull. Exp. Biol. Med . 164 (2): 177–180. doi :10.1007/s10517-017-3952-2 . PMID 29181662 .
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
AMPAR Tooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor KAR Tooltip Kainate receptor NMDAR Tooltip N-Methyl-D-aspartate receptor
Group I
mGluR1 Tooltip Metabotropic glutamate receptor 1 mGluR5 Tooltip Metabotropic glutamate receptor 5
Group II
mGluR2 Tooltip Metabotropic glutamate receptor 2 mGluR3 Tooltip Metabotropic glutamate receptor 3
Group III
mGluR4 Tooltip Metabotropic glutamate receptor 4 mGluR6 Tooltip Metabotropic glutamate receptor 6 mGluR7 Tooltip Metabotropic glutamate receptor 7 mGluR8 Tooltip Metabotropic glutamate receptor 8
Forms Targets
NO donors (prodrugs ) Enzyme (inhibitors )
Others
Indirect/downstream NO modulators: ACE inhibitors /AT-II receptor antagonists (e.g., captopril , losartan )ETB receptor antagonists (e.g., bosentan )L-Type calcium channel blockers (e.g., dihydropyridines : nifedipine )Nebivolol (beta blocker )PDE5 inhibitors (e.g., sildenafil )non-selective PDE inhibitors (e.g., caffeine )
PDE9 inhibitors (e.g., paraxanthine )
cGMP preferring PDE inhibitors (e.g., sildenafil, paraxanthine, tadalafil)
Statins (e.g., simvastatin )
