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 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CA1 pyramidal cells
100 and 300 µM
increased the sIPSC frequency and amplitude
Cells. 2022 Sep 27;11(19):3015
Mouse cortical glutamatergic synaptosomes
0.1 μM
90 seconds
LY367385 significantly reinforced the inhibitory effect exerted by 1 mM (RS)-baclofen on the 12 mM KCl-evoked overflow of preloaded [3H]D-aspartate
Front Mol Neurosci. 2018 Sep 18;11:324
Mouse cortical GABAergic synaptosomes
0.03–1 μM
90 seconds
LY367385 significantly amplified the 3 mM (RS)-baclofen-induced inhibition of [3H]GABA overflow evoked by 12 mM KCl
Front Mol Neurosci. 2018 Sep 18;11:324
CA1 pyramidal cells
300 µM
increased the sIPSC frequency and amplitude, effects reverted by CB1 receptor agonists
Cells. 2022 Sep 27;11(19):3015
LY367385 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
CA1 O-LM interneurons
Brain slice pre-incubation
100 μM
15-30 min pre-incubation
LY367385 significantly attenuated the peak amplitude of DHPG-induced depolarization and the number of slow oscillations, indicating that mGluR1 plays a major role in slow oscillations in CA1 O/A interneurons.
Neuropharmacology. 2018 Sep 1;139:150-162
Rats
Cocaine self-administration model
In vitro tissue culture
50 µM
1 hour
LY367385 did not influence overall translation
Biol Psychiatry. 2018 Aug 1;84(3):223-232
Mongolian gerbils (Meriones unguiculatus)
Global ischemia model
Transdialytic perfusion
1 mM
Increased the hippocampal release of GABA and protected CA1 pyramidal cells against post-ischemic injury
Cells. 2022 Sep 27;11(19):3015
Rats
Pentylenetetrazole-induced status epilepticus model
Intracerebroventricular injection
320 nmol/10 μL
Single dose
LY367385 alleviated the severity of pentylenetetrazole-induced status epilepticus
Neural Regen Res. 2023 Mar;18(3):594-602
Japanese quail
Castrated, testosterone-treated males
Intracerebroventricular injections
100 μg
Single injection, 30 min before testing
LY367385 significantly inhibited male sexual motivation in Japanese quail, while mGluR2/3 and mGluR5 antagonists were ineffective. Additionally, LY367385 blocked the behavioral restoration induced by E2 or DPN, providing functional evidence that ERβ interacts with metabotropic glutamate receptor 1a (mGluR1a) signaling to acutely regulate male sexual motivation.
J Neurosci. 2015 Sep 23;35(38):13110-23
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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