Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice

The protection of pyroglutamic acid and derivs. (I, R = CH2C≡CH, CH2CH:CH2, CH2Ph, CH2C6H4Cl-​p, CH2C6H4CN-​p, as Me) (injected i.p.) against glutamate- and NMDA (N-​methyl-​D-​aspartate) (i.c.v.) induced seizures in mice has been studied in comparison with known antiepileptics and antagonists of excitatory amino acids. The potency of pyroglutamic acid and some derivs. (Id,​f,​g,​h) against glutamate-​induced convulsions was similar to that shown by di-​Et glutamate and by valproic acid. Interestingly, pyroglutamic acid did not affect NMDA-​induced convulsions which were well antagonized by both 2-​amino-​5-​phosphonoaleric acid and by diazepam. Thus, pyroglutamic acid may represent the starting material for synthesis of excitatory amino acid antagonists acting at non NMDA receptors.