GYKI 53405

GYKI 53405 (LY 293606) is a non-competitive, orally active AMPA receptor antagonist. GYKI 53405 shows no significant binding affinity for GABA_A, GABA_B or benzodiazepine receptors. GYKI 53405 increases self-grooming behavior, induces wet dog-like shakes, reduces spontaneous activity, produces anxiolytic-like behavior, reverses the anxiogenic effect induced by mCPP, inhibits locomotor activity, suppresses sound-induced and maximal electroshock-induced seizures, prolongs survival in global cerebral ischemia models, and exhibits sustained anticonvulsant effects at doses below the sedation threshold. GYKI 53405 can be used in research related to absence epilepsy, anxiety disorders and global cerebral ischemia^[1][2][3]. In Vitro:GYKI 53405 inhibits kainate-induced whole-cell currents in primary cultured embryonic telencephalic cells of Sprague-Dawley rats, with an IC₅₀ of 7.4 μM^[2].
GYKI 53405 inhibits the amplitude of AMPA receptor-mediated population spike potentials in CA1 pyramidal cells of hippocampal slices from male Wistar rats, with an IC₅₀ of 17.8 μM^[2].
GYKI 53405 (10^-7 M) exhibits no significant binding affinity for GABA_A, GABA_B or benzodiazepine receptors at a concentration of 10^-7 M^[2]. In Vivo:GYKI 53405 (16 mg/kg; i.p.; single administration) fails to significantly alter spike-and-wave discharges and wakefulness in WAG/Rij rats with genetic absence epilepsy, nor does it induce adverse neurobehavioral effects^[1].
GYKI 53405 (3 mg/kg; p.o.; single dose) induces anxiolytic-like behavior in male Sprague-Dawley rats in the elevated plus maze test^[2].
GYKI 53405 (3 mg/kg; i.p.; single administration) reverses mCPP-induced anxiety-like behavior in male Wistar rats in the light-dark box test^[2].
Oral administration of GYKI 53405 produces sedative effects in male NMRI mice, with an ID₅₀ of 9.8 mg/kg^[2].
GYKI 53405 (i.p.; single administration) exhibits potent anticonvulsant activity in audiogenic seizure-susceptible DBA/2j mice, with an ED₅₀ value of 1.1 mg/kg for inhibiting tonic extension seizures and an ED₅₀ value of 3.1 mg/kg for inhibiting clonic seizures^[3].
GYKI 53405 (i.p.; single dose; 30 min prior to electroshock) inhibits maximal electroshock-induced tonic hindlimb extension seizures in NMRI mice, with an i.p. ED₅₀ of 2.6 mg/kg^[3].
GYKI 53405 (3.75-30 mg/kg; i.p.; single administration; 30 minutes prior to MgCl₂ injection) exerts dose-dependent neuroprotective activity in the MgCl₂-induced global cerebral ischemia model of NMRI mice, with a PD₅₀ of 8.3 mg/kg via intraperitoneal injection, and significantly prolongs the survival time of mice starting from the dose of 7.5 mg/kg^[3].