No abstract

No abstract

No abstract

In the brain, canonical excitatory neurotransmission is mediated by L-glutamate and its ionotropic (iGluR) and metabotropic (mGluR) receptors. The wide diversity of these often limits the development of glutamatergic drugs. This is due to the arduousness of achieving selectivity with specific ligands. In the present article, encouraged by reports of bioactive organoboron compounds, a diphenylboroxazolidone derived from quinolinate (BZQuin) was evaluated. BZQuin was synthesized with a yield of 87%. Its LD50 was 174 mg/kg in male CD-1 mice, as estimated by a modified Lorke’s method. BZQuin exerted a reduced ability to cause seizures when compared against its precursor, quinolinate. The latter suggested that it does not directly stimulate the ionotropic NMDA receptors or other ionic channels. The observation that the antiglutamatergic drugs riluzole and memantine displaced the BZQuin effect left the mGluRs as their possible targets. This is in line with results from molecular-docking simulations. During these simulations, BZQuin bound only to orthosteric sites on mGluR1, mGluR2, and mGluR7, with higher affinity than quinolinate. The survival of the neurons of mice previously administered with BZQuin or quinolinate was quantified in four neuroanatomical structures of the brain. The BZQuin effect was more appreciable in brain regions with a high expression of the previously mentioned mGluRs, while both antiglutamatergic drugs exerted a neuroprotective effect against it. Together, these results suggest that BZQuin exerts a positive influence on glutamatergic neurotransmission while selectively interacting with certain mGluRs.