Glufimet |
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Other names | RGPU-238; Dimethyl 3-phenylglutamic acid hydrochloride; Dimethyl 3-phenylglutamate hydrochloride; 1,5-Dimethyl (2S)-2-amino-3-phenylpentanedioate hydrochloride |
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dimethyl 2-amino-3-phenylpentanedioate;hydrochloride
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CompTox Dashboard (EPA) | |
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Formula | C13H18ClNO4 |
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Molar mass | 287.74 g·mol−1 |
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3D model (JSmol) | |
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COC(=O)CC(C1=CC=CC=C1)C(C(=O)OC)N.Cl
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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
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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] It contains phenibut and 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] It has been suggested that 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]
See also
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". Bulletin of Experimental Biology and Medicine. 159 (3): 384–6. doi:10.1007/s10517-015-2969-7. PMID 26205724. S2CID 666113.
- ^ 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". Bulletin of Experimental Biology and Medicine. 163 (2): 226–229. doi:10.1007/s10517-017-3772-4. PMID 28726197. S2CID 4907409.
- ^ 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]". Advances in Gerontology (in Russian). 29 (1): 116–122. doi:10.1134/S2079057016030073. PMID 28423256. S2CID 78111848.
- ^ 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". Bulletin of Experimental Biology and Medicine. 164 (2): 177–180. doi:10.1007/s10517-017-3952-2. PMID 29181662. S2CID 90334012.
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Ionotropic | GABAATooltip 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 (123I)
- 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
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GABAA-ρTooltip γ-Aminobutyric acid A-rho receptor | |
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Metabotropic | GABABTooltip γ-Aminobutyric acid B receptor |
- Negative modulators: Compound 14
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- See also
- Receptor/signaling modulators
- GABAA receptor positive modulators
- GABA metabolism/transport modulators
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AMPARTooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor | |
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KARTooltip Kainate receptor | |
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NMDARTooltip N-Methyl-D-aspartate receptor | |
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- See also: Receptor/signaling modulators
- Metabotropic glutamate receptor modulators
- Glutamate metabolism/transport modulators
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Group I | mGluR1Tooltip Metabotropic glutamate receptor 1 | |
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mGluR5Tooltip Metabotropic glutamate receptor 5 | |
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Group II | mGluR2Tooltip Metabotropic glutamate receptor 2 | |
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mGluR3Tooltip Metabotropic glutamate receptor 3 | |
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Group III | mGluR4Tooltip Metabotropic glutamate receptor 4 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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mGluR6Tooltip Metabotropic glutamate receptor 6 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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mGluR7Tooltip Metabotropic glutamate receptor 7 |
- Antagonists: CPPG
- MAP4
- MMPIP
- MPPG
- MSOP
- MTPG
- UBP-1112
- XAP044; Negative allosteric modulators: ADX71743
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mGluR8Tooltip Metabotropic glutamate receptor 8 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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See also: Receptor/signaling modulators • Ionotropic glutamate receptor modulators • Glutamate metabolism/transport modulators |
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Forms | |
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Targets | |
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NO donors (prodrugs) |
- NONOates (diazeniumdiolates): Diethylamine/NO (DEA/NO)
- Diethylenetriamine/NO (DETA/NO)
- GLO/NO
- JS-K
- Methylamine hexamethylene methylamine/NO (MAHMA/NO)
- PROLI/NO
- Spermine/NO (SPER/NO)
- V-PYRRO/NO
- Unsorted: Cimlanod
- FK-409
- FR144220
- FR146881
- N-Acetyl-N-acetoxy-4-chlorobenzenesulfonamide
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Enzyme (inhibitors) | NOS | nNOS | |
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iNOS |
- 1-Amino-2-hydroxyguanidine
- 2-Ethylaminoguanidine
- 2-Iminopiperidine
- 1400W
- AEITU
- Aminoguanidine (pimagedine)
- AMT
- AR-C 102222
- BYK-191023
- Canavanine
- Cindunistat (SD-6010)
- EITU
- IPTU
- MITU
- N5-(1-Iminoethyl)-L-ornithine (L-NIO)
- N6-(1-Iminoethyl)-L-lysine (L-NIL)
- Nω-Methyl-L-arginine (L-NMA)
- Ronopterin (VAS-203)
- TRIM
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eNOS | |
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Unsorted | |
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Arginase | |
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CAMK | |
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Others |
- Precursors: L-Arginine
- Nω-Hydroxy-L-arginine (NOHA)
- 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)
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See also: Receptor/signaling modulators |