GYKI 53784
GYKI 53784 (LY303070) is an orally active, blood-brain penetrant, selective, non-competitive AMPA receptor antagonist (IC50 = 0.32 μM). GYKI 53784 completely blocks AMPA-mediated synaptic transmission, protects against excitotoxicity, and partially inhibits Kainite (Kainic acid) (HY-N2309) responses, revealing both AMPA and kainate receptors. GYKI 53784 selectively blocks synaptic transmission (IC50 = 365.3 nM) without affecting neuronal excitability, and exhibits potent stereoselective antinociceptive effects via an opioid-independent mechanism. GYKI 53784 is a versatile tool for studying AMPA receptor function in synaptic transmission, excitotoxicity, neuroprotection, pain, and inflammation, with potential relevance to hearing loss, neonatal ischemia, neurodegenerative disorders, schizophrenia, and Alzheimer's disease.
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- CAS. Nr.: 161832-71-9
- Formel: C19H20N4O3
- Molecular Weight:352.39
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
Beschreibung
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AMPA Receptor 0.32 μM (IC50) |
In Vitro
GYKI 53784 (10 mM; 23-120 nA) microionophoretically blocks kainate-induced depolarization (AMPA-mediated under ketamine-diazepam alone), but pentobarbitone reverses this block and confers AMPA-versus-kainate selectivity; both effects require continuous pentobarbitone and are washout-reversible[1].
GYKI 53784 (0.1-160 μM; perfusion; 10 min) selectively blocks AMPA-mediated auditory nerve transmission (hair cell-sparing) and NMDA (HY-17551) does not mediate fast cochlear signaling[2].
GYKI 53784 (10-100 μM; perfusion; 10 min) sensitivity of auditory nerve fibers correlates with postsynaptic AMPA receptor density and blocks AMPA/kainate-induced cochlear excitotoxicity[2].
GYKI 53784 (50 μM; perfusion; 20 min) blocks AMPA/kainate-induced cochlear excitotoxicity[2].
GYKI 53784 (50 μM; perfusion; 20 min) blocks Eticlopride (HY-121129)-induced excitotoxicity by AMPA receptor antagonism, confirming that loss of dopaminergic inhibition triggers AMPA-mediated dendritic damage[3].
GYKI 53784 (LY303070) (10 μM) selectively blocks AMPA receptor-mediated synaptic transmission (IC50 = 365.3 nM) in cultured rat cortical neurons without affecting direct neuronal excitability[4].
GYKI 53784 (10 μM) effectively isolates kainate receptor-mediated currents in cerebellar granule neurons, almost completely blocking the AMPA receptor component while preserving kainate receptor function[5].
GYKI 53784 (0.01-10 μM) concentration-dependently inhibits the steady-state current induced by AMPA, with an IC50 of 0.32 μM in rat cerebellar Purkinje cells[6].
GYKI 53784 (0.01 mM) inhibits AMPA-induced 3H-GABA release in a non-competitive manner[7].
GYKI 53784 (5-20 μM) completely blocks AMPA-mediated synaptic transmission in brainstem motoneurons but only partially suppresses kainate responses[9].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GYKI 53784 (2 mg/kg; i.p.; every one hour; for 4 times) exerts significant neuroprotective effects against AMPA-induced striatal damage in neonatal rats and effectively suppresses AMPA-induced turning behavior and seizure-like activity[8].
GYKI 53784 (0.01-30 mg/kg; p.o.; single dose) potently suppresses chemical visceral pain in a stereospecific manner[10].
GYKI 53784 (0.003-3 mg/kg; p.o.; single dose) exhibits potent antinociceptive effects in the rat tail flick test in a stereospecific manner[10].
GYKI 53784 (0.01 mg/kg; p.o.; single dose) shows no significant synergy with morphine in SPRD rats, and its antinociceptive effect is not antagonized by Naloxone (HY-17417A), indicating that its action does not involve opioid receptor mechanisms[10].
GYKI 53784 (1-10 mg/kg; p.o.; single dose) has moderate anti-inflammatory effects at high doses in SPRD rats[10].
GYKI 53784 (10 mg/kg; p.o.; single dose) exhibits anti-inflammatory effects in the mouse Zymosan (Zymosan A) (HY-W250113)-induced paw edema model[10].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Adult Sprague–Dawley rats weighing 220-300 g[1]
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Dosage:2.3 mg/kg
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Administration:i.v., single dose
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Result:Exerted no significant effect on intrinsic membrane properties of abducens motoneurons.
Reversibly depressed trigeminal-evoked EPSPs following intravenous administration.
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Animal Model:7-day-old neonatal SPRD breed rats weighing 16-21 g[8]
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Dosage:2 mg/kg
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Administration:i.p.; every one hour; for 4 times
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Result:Significantly inhibited AMPA-induced abnormal rotational movements and seizure-like seizures in newborn rats.
Reduced AMPA-induced striatal tissue damage.
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Animal Model:Male mice of the CD1 strain weighing 20-25 g[10]
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Dosage:0.01-30 mg/kg
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Administration:p.o., single dose
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Result:Dose-dependently suppressed phenylquinone-induced writhing, with an ED50 of 0.51 mg/kg.
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Animal Model:SPRD (Sprague-Dawley) rats weighing 150-200 g[10]
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Dosage:0.003 mg/kg, 0.3 mg/kg, 3 mg/kg
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Administration:p.o., single dose
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Result:Dose-dependently prolonged tail flick latency, with peak effect at 15 min post-administration and an ED50 of 0.02 mg/kg.
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Animal Model:SPRD (Sprague-Dawley) rats weighing 150-200 g[10]
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Dosage:0.01 mg/kg combined with increasing doses of morphine
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Administration:p.o.,combined with morphine (s.c.), single dose
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Result:Had no significant effect on the ED50 of morphine.
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Animal Model:SPRD (Sprague-Dawley) rats weighing 150-200 g[10]
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Dosage:1-10 mg/kg
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Administration:p.o., single dose
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Result:Significantly (though moderately) inhibited Carrageenan (λ-Carrageenan) (HY-N9470)-induced paw edema (max ~25-30%), peaking at 2-3 h after injection.
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Animal Model:Male mice of the CD1 strain weighing 20-25 g[10]
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Dosage:10 mg/kg
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Administration:p.o., single dose
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Result:Significantly inhibited zymosan-induced paw edema.
Chemical Information
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CAS. Nr. 161832-71-9
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Molecular Weight 352.39
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Formel C19H20N4O3
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SMILES
CNC(N1N=C(C2=CC=C(C=C2)N)C3=C(C[C@H]1C)C=C4C(OCO4)=C3)=O
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Synonyms
LY303070
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Ruiz A, et al. Modulation of kainate-induced responses by pentobarbitone and GYKI 53784 in rat abducens motoneurons in vivo. Brain Res. 1999 Feb 13;818(2):421-30. [Content Brief]
[2]. Ruel J, et al. The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea. Neuropharmacology. 2000 Aug 23;39(11):1959-73. [Content Brief]
[3]. Ruel J, et al. Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea. Eur J Neurosci. 2001 Sep;14(6):977-86. [Content Brief]
[4]. Virdee JK, et al. A high-throughput model for investigating neuronal function and synaptic transmission in cultured neuronal networks. Sci Rep. 2017 Nov 3;7(1):14498. [Content Brief]
[5]. Valenzuela CF, et al. Acute effects of ethanol on pharmacologically isolated kainate receptors in cerebellar granule neurons: comparison with NMDA and AMPA receptors. J Neurochem. 1998 Oct;71(4):1777-80. [Content Brief]
[6]. Kapus G, et al. Differential modulation of the GYKI 53784-induced inhibition of AMPA currents by various AMPA-positive modulators in cerebellar Purkinje cells. Eur J Pharmacol. 2000 May 26;397(1):43-7. [Content Brief]
[7]. Harsing LG Jr, et al. Negative allosteric modulators of AMPA-preferring receptors inhibit [(3)H]GABA release in rat striatum. Neurochem Int. 2000 Jul;37(1):33-45. [Content Brief]
[8]. Világi I, et al. Protective effect of the antiepileptic drug candidate talampanel against AMPA-induced striatal neurotoxicity in neonatal rats. Brain Res Bull. 2002 Oct 15;59(1):35-40. [Content Brief]
[9]. Launey T, et al. Excitatory amino acids and synaptic transmission in embryonic rat brainstem motoneurons in organotypic culture. Eur J Neurosci. 1999 Apr;11(4):1324-34. [Content Brief]
[10]. Székely JI, et al. Apparent antinociceptive and anti-inflammatory effects of GYKI 52466. Eur J Pharmacol. 1997 Oct 8;336(2-3):143-54. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
GYKI 53784 Related Classifications
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