LY367385 is a highly effective and selective mGluR1a antagonist. LY367385 has neuroprotective, anticonvulsant, and antiepileptic effects. Compared with > 100 μM for mGlu5a, LY367385 has an IC50 of 8.8 μM for inhibits of quisqualate-induced phosphoinositide (PI) hydrolysis.

mGluR1a:8.8 μM

LY367385 shows greater efficacy than LY367366 and neither of these compounds influenced neuronal viability per se and it also displays effective neuroprotective effects, causing a 50% reduction in (S)-3,5-Dihydroxyphenylglycine (DHPG) potentiation at a concentration of 10 nM. LY367385 combined with N-methyl-D-aspartate (NMDA) during the toxic pulse decreases neuronal degeneration in a concentration-dependent fashion, with a maximal reduction of NMDA toxicity ranging from 40 to 60%. LY367385 fully antagonized the amplification of NMDA toxicity by DHPG under experimental conditions at higher concentrations of the antagonist[2].

LY367385 produces a rapid, transient suppression of sound-induced clonic seizures (ED50 = 12 nM, i.c.v., 5 min), in DBA/2 mice. LY367385 significantly decreases the incidence of spontaneous spike and wave discharges on the electroencephalogram in lethargic mice, from 30 to >150 min after the administration of LY367385, 250 nM, i.c.v. LY367385 has been administered intracerebroventricularly (i.c.v.) to DBA/2 mice and lethargic mice (lh/lh), and focally into the inferior colliculus of genetically epilepsy prone rats (GEPR). LY367385 reduces sound-induced clonic seizures, in genetically epilepsy prone rats. LY367385, 160 nM bilaterally, fully suppresses clonic seizures after 2-4 h[3].