GYKI-52,466
GYKI-52466 is a 2,3-benzodiazepine that acts as an ionotropic glutamate receptor antagonist, which is a non-competitive AMPA receptor antagonist (IC50 values are 10-20, ~ 450 and >> 50 μM for AMPA- , kainate- and NMDA-induced responses respectively), orally-active anticonvulsant, and skeletal muscle relaxant. Unlike conventional 1,4-benzodiazepines, GYKI-52466 and related 2,3-benzodiazepines do not act on GABAA receptors. Like other AMPA receptor antagonists, GYKI-52466 has anticonvulsant and neuroprotective properties.
References
- ↑ Donevan, S.D., Rogawski, M.A., Allosteric regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors by thiocyanate and cyclothiazide at a common modulatory site distinct from that of 2,3-benzodiazepines. Neuroscience 87, 615, (1998)
- ↑ Donevan, S.D., Rogawski, M.A., GYKI 52466, a 2,3-benzodiazepine is a highly selective, non-competitive antagonist of AMPA/kainate receptor responses. Neuron 10, 51, (1993)
- ↑ Wilding, T.J., Huettner, J.E., Differential antagonism of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-preferring and kainate-preferring receptors by 2,3-benzodiazepines. Mol. Pharmacol. 47, 582, (1995)
- ↑ Tarnawa et al. (1989) Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466. Eur. J.Pharmacol. 167 193
- ↑ Paternain et al. (1995) Selective antagonism of AMPA receptors unmasks kainate receptor-mediated responses in hippocampal neurons. Neuron 14 185.
- ↑ Rzeski et al. (2001) Glutamate antagonists limit tumor growth. Proc. Natl.Acad. Sci.USA 98 6372.
- ↑ Szabados et al. (2001) Comparison of anticonvulsive and acute neuroprotective activity of three 2,3-benzodiazepine compounds, GYKI 52466, GYKI 53405, and GYKI 53655. Brain Res. Bull. 55 387.
Glutamatergics |
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| Receptor (ligands) | AMPA | |
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| NMDA |
- Antagonists: Competitive antagonists: AP5 (APV)
- AP7
- CGP-37849
- CGP-39551
- CGP-39653
- CGP-40116
- CGS-19755
- CPP
- LY-233,053
- LY-235,959
- LY-274,614
- MDL-100,453
- Midafotel (d-CPPene)
- NPC-12,626
- NPC-17,742
- PBPD
- PEAQX
- Perzinfotel
- PPDA
- SDZ-220581
- Selfotel; Noncompetitive antagonists: ARR-15,896
- Caroverine
- Dexanabinol
- FPL-12495
- FR-115,427
- Hodgkinsine
- Magnesium
- MDL-27,266
- NPS-1506
- Psychotridine
- Zinc; Uncompetitive pore blockers: 2-MDP
- 3-MeO-PCP
- 8A-PDHQ
- 18-MC
- α-Endopsychosin
- Alaproclate
- Amantadine
- Aptiganel
- ARL-12,495
- ARL-15,896-AR
- ARL-16,247
- Budipine
- Conaridine
- Delucemine
- Dexoxadrol
- Dextrallorphan
- Dieticyclidine
- Dizocilpine
- Esketamine
- Etoxadrol
- Eticyclidine
- Gacyclidine
- Ibogaine
- Ibogamine
- Indantadol
- Ketamine
- Ketobemidone
- Lanicemine
- Loperamide
- Memantine
- Methadone (Levomethadone)
- Methorphan (Dextromethorphan
- Levomethorphan)
- Methoxetamine
- Methoxphenidine
- Milnacipran
- Morphanol (Dextrorphan
- Levorphanol)
- NEFA
- Neramexane
- Nitromemantine
- Nitrous oxide
- Noribogaine
- Orphenadrine
- PCPr
- Pethidine (meperidine)
- Phencyclamine
- Phencyclidine
- Propoxyphene
- Remacemide
- Rhynchophylline
- Rimantadine
- Rolicyclidine
- Sabeluzole
- Tabernanthine
- Tenocyclidine
- Tiletamine
- Tramadol
- Xenon; Glycine site antagonists: 7-CKA
- ACC
- ACEA-1011
- ACEA-1328
- AV-101
- Carisoprodol
- CGP-39653
- CNQX
- DCKA
- DNQX
- Felbamate
- Gavestinel
- GV-196,771
- Kynurenic acid
- L-689,560
- L-701,324
- Licostinel (ACEA-1021)
- LU-73,068
- MDL-105,519
- Meprobamate
- MRZ 2/576
- PNQX
- ZD-9379; NR2B subunit antagonists: Besonprodil
- CERC-301 (MK-0657)
- CO-101,244 (PD-174,494)
- Eliprodil
- Haloperidol
- Ifenprodil
- Isoxsuprine
- Nylidrin
- Ro8-4304
- Ro25-6981
- Traxoprodil; Polyamine site antagonists: Arcaine
- Co 101676
- Diaminopropane
- Diethylenetriamine
- Huperzine A
- Putrescine
- Ro 25-6981; Unclassified/unsorted antagonists: Bumetanide
- Chloroform
- Cyclopropane
- D-αAA
- Diethyl ether
- Diphenidine
- Enflurane
- Ethanol
- Flufenamic acid
- Flupirtine
- Furosemide
- Halothane
- Isoflurane
- Metaphit
- Methoxyflurane
- Niflumic acid
- Piretanide
- Toluene
- Trichloroethane
- Trichloroethanol
- Trichloroethylene
- Xylene
|
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| Kainate | |
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| mGlu1 |
- Antagonists: BAY 36-7620
- CPCCOEt
- LY-367,385
- LY-456,236
- MCPG
- NPS-2390
|
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| mGlu2 | |
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| mGlu3 | |
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| mGlu4 |
- Agonists: Glutamate
- L-AP4
- PHCCC
- VU-001,171
- VU-0155,041; Positive allosteric modulators: MPEP
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
|
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| mGlu5 | |
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| mGlu6 |
- Agonists: Glutamate
- L-AP4
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
|
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| mGlu7 |
- Antagonists: CPPG
- MAP4
- MMPIP
- MPPG
- MSOP
- MTPG
- UBP-1112
|
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| mGlu8 |
- Antagonists: CPPG
- MAP4
- MPPG
- MSOP
- MTPG
- UBP-1112
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| Transporter (blockers) | |
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| Enzyme (inhibitors) | GAH | |
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| AST |
- 2-Amino-3-butenoic acid
- AAOA
- AMB
- β-DL-Methylene-aspartate
- Hydrazinosuccinate
|
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| ALT |
- β-Chloro-L-alanine
- L-Cycloserine
- Propargylglycine
|
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| GDH | |
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| GS |
- 2-Aminoadipic acid
- JFD01307SC
- Methionine sulfoximine
- Phosphinothricin (glufosinate)
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| GAD | |
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| Others |
- Cofactors: α-Ketoglutaric acid
- Iron
- Sulfur
- Vitamin B2
- Vitamin B3
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| See also: GABAergics • GHBergics • Glycinergics |
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| 1,4-Benzodiazepines | |
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| 1,5-Benzodiazepines | |
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| 2,3-Benzodiazepines* | |
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| Triazolobenzodiazepines | |
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| Imidazobenzodiazepines | |
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| Oxazolobenzodiazepines | |
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| Thienodiazepines | |
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| Pyridodiazepines | |
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| Pyrazolodiazepines | |
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| Pyrrolodiazepines | |
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| Tetrahydroisoquinobenzodiazepines | |
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| Pyrrolobenzodiazepines* |
- Anthramycin
- Mazethramycin
- Porothramycin
- Sibiromycin
- Tomaymycin
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| Benzodiazepine prodrugs | |
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