Neurolathyrism is a human motoneuron disease caused by the overconsumption of grass pea ( Lathyrus sativus ) that contains a toxic non-protein amino acid, 3- N -oxalyl- L -2,3-diaminopropanoic acid ( L -β-ODAP). The preventive activities of various glutamatergic agents from acute neuronal death caused by L -β-ODAP were studied using rat primary cortical neuron/glia culture. Nearly 80% of the rat primary cortical neurons were killed by 300 μ M L -β-ODAP within 24 h. Though antagonists acting on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor prevented most of the toxicity, antagonists acting on group I metabotropic glutamatergic receptors (mGluRs), including ( RS )-1-aminoindan-1,5-dicarboxylic acid (AIDA), ( S )-α-methyl-4-carboxyphenylglycine (MCPG), and 2-methyl-6-(2-phenylethenyl)pyridine (SIB1893) partially and significantly prevented neuronal death due to L -β-ODAP. These antagonists, within limited concentrations, did not have any inhibitory effects on the currents through AMPA receptors expressed in Xenopus oocytes. L -β-ODAP itself did not induce the currents through group I mGluRs expressed in Xenopus oocytes. These results suggest that the neurotoxicity induced by L -β-ODAP is partially mediated by the activation of group I mGluRs by an indirect mechanisms.