GYKI 52466 (hydrochloride)

GYKI 52466 is an allosteric AMPA receptor antagonist.¹ It selectively inhibits AMPA-induced inward currents (IC₅₀ = 7.5 µM) over NMDA- or GABA-induced inward currents in primary rat hippocampal neurons at 50 µM but also inhibits kainate-induced inward currents in the same cells (IC₅₀ = 11 µM).² GYKI 52466 (10 µM) reduces the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in the same cells. It increases the latency to seizure onset and reduces mortality in a rat model of generalized tonic-clonic seizures induced by 4-aminopyridine when administered at doses of 25 and 50 mg/kg.¹ GYKI 52466 (30 mg/kg) prevents neuronal damage in the CA1 region of the hippocampus in a rat model of global ischemia-reperfusion injury induced by four-vessel occlusion.³

1.Weiczner, R., Krisztin-PÉva, B., and MihÁly, A.Blockade of AMPA-receptors attenuates 4-aminopyridine seizures, decreases the activation of inhibitory neurons but is ineffective against seizure-related astrocytic swellingEpilepsy Res.78(1)22-32(2008) 2.Donevan, S.D., and Rogawski, M.A.GYKI 52466, a 2,3-benzodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responsesNeuron10(1)51-59(1993) 3.Block, F., Schmitt, W., and Schwarz, M.Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in ratsJ. Neurol. Sci.139(2)167-172(1996)