LY367385 HCl is a highly selective and potent mGluR1a antagonist. The IC50 for inhibition of quisqualate-induced hydrolysis of phosphatidylinositol (PI) by LY367385 HCl was 8.8 μM, whereas that for inhibition of mGlu5a was greater than 100 μM. LY367385 HCl is known to show neuroprotective, anticonvulsant, and anti-epileptic effects[1][2].During the toxic pulse period, LY367385 HCl combined with NMDA can reduce neuronal degeneration in a concentration-dependent manner, with the maximum reduction in NMDA toxicity ranging from 40% to 60%. LY367385 is more potent than LY367366, and neither compound by itself affects neuronal viability. LY367385 HCl exhibits potent neuroprotective effects, reducing the synergistic effect of (S)-3,5-Dihydroxyphenylglycine (DHPG) by 50% at a concentration of 10 nM. Under experimental conditions with higher concentrations of antagonists, LY367385 HCl can completely antagonize the amplifying effect of DHPG on NMDA toxicity [2].
LY367385 HCl 动物研究
Animal study
LY367385 HCl can be used for intracerebroventricular injections (i.c.v.) in DBA/2 mice and lethargic mice (lh/lh), as well as focally in the inferior colliculus of genetically epilepsy-prone rats (GEPR). In DBA/2 mice, LY367385 HCl rapidly and transiently suppressed sound-induced clonic seizures with an ED50 value of 12 nM (i.c.v., 5 min). In lethargic mice, LY367385 HCl significantly reduced the incidence of spontaneous spikes and wave-like discharges on the EEG, ranging from 30 to 150 minutes after administration of LY367385 (250 nM, i.c.v)[3].
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