LY 379268 is a highly selective group II mGlu receptor agonist with EC50 value of 2.69 and 4.48 nM for hmGlu2 and hmGlu3, respectively [1].
mGluRs is a type of glutamate receptor that is being considered as targets for the therapeutic intervention in neurodegenerative disorders. Activation of Group II mGluRs can protect cultured neurones against excitotoxic damage by inhibiting glutamate release [1].
In the CA1 hippocampal cells, LY379268 reduced the ischemia-induced hyperactivity and provided protection after 5-min bilateral carotid artery occlusion (BCAO). Furthermore, before 5-min BCAO, 24- or 48-h pretreatment with LY379268 educed the damage to CA1 hippocampal neurons in a gerbil model [2].
In the gerbil bilateral occlusion of the carotid artery, LY379268 prevented the loss of CA1 hippocampal neurones. Also, LY379268 decreased the BCAO-induced increase in TUNEL positive cells. In the rat model, LY379268 didn’t affect the size of the infarct following middle cerebral artery occlusion (MCAO) [1].
References:
[1]. Bond A, Ragumoorthy N, Monn JA, et al. LY379268, a potent and selective Group II metabotropic glutamate receptor agonist, is neuroprotective in gerbil global, but not focal, cerebral ischaemia. Neurosci Lett, 1999, 273(3): 191-194.
[2]. Bond A, Jones NM, Hicks CA, et al. Neuroprotective effects of LY379268, a selective mGlu2/3 receptor agonist: investigations into possible mechanism of action in vivo. J Pharmacol Exp Ther, 2000, 294(3): 800-809.