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 GABA_A receptors. Like other AMPA receptor antagonists, GYKI-52466 has anticonvulsant and neuroprotective properties.

GYKI-52,466[1][2][3][4][5][6][7]

Names
IUPAC name 4-(8-methyl-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-5-yl)aniline
Identifiers
CAS Number	102771-26-6^Y 192065-56-8 (HCl salt)^N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:79560^N
ChEMBL	ChEMBL275006^N
ChemSpider	3417^N
ECHA InfoCard	100.162.378
IUPHAR/BPS	4210
KEGG	C15040^N
PubChem CID	3538
UNII	471V8NZ5X3^N
CompTox Dashboard (EPA)	DTXSID40145500
InChI InChI=1S/C17H15N3O2/c1-10-6-12-7-15-16(22-9-21-15)8-14(12)17(20-19-10)11-2-4-13(18)5-3-11/h2-5,7-8H,6,9,18H2,1H3^N Key: LFBZZHVSGAHQPP-UHFFFAOYSA-N^N InChI=1/C17H15N3O2/c1-10-6-12-7-15-16(22-9-21-15)8-14(12)17(20-19-10)11-2-4-13(18)5-3-11/h2-5,7-8H,6,9,18H2,1H3 Key: LFBZZHVSGAHQPP-UHFFFAOYAH
SMILES CC1=NN=C(C2=CC3=C(C=C2C1)OCO3)C4=CC=C(C=C4)N
Properties
Chemical formula	C17H15N3O2
Molar mass	293.32 g/mol
Appearance	Yellow solid (HCl salt)
Density	1.393 g/cm^3
Solubility in water	>10 mg/mL (HCl salt)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is ^YN ?)
Infobox references

See also

• GYKI-52895, another 2,3-benzodiazepine with other than GABAergic function
• Tifluadom
• Lufuradom

References

1. 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)
2. 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)
3. 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)
4. Tarnawa et al. (1989) Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466. Eur. J.Pharmacol. 167 193
5. Paternain et al. (1995) Selective antagonism of AMPA receptors unmasks kainate receptor-mediated responses in hippocampal neurons. Neuron 14 185.
6. Rzeski et al. (2001) Glutamate antagonists limit tumor growth. Proc. Natl.Acad. Sci.USA 98 6372.
7. 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.