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^{[1][2][3][4][5][6][7][8][9][10]}. 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].
In Vivo:GYKI 53784 (LY303070) (2.3 mg/kg; i.v.; single dose) has no direct effect on passive/active membrane electrical properties of motoneurons in Sprague–Dawley rat; its inhibitory effect is specific to AMPA receptor-mediated excitatory synaptic transmission^[1].
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].