Decrease in the glutamate release may contribute to the neuroprotective action of the novel neuroleptic drug dilept

: Dilept (GZR-123, N-caproyl-L-prolyl-L-tyrosine methyl ester), designed and synthesized at the Zakusov Institute of Pharmacology, was chosen as one of the most effective compounds from a series of N-acylprolyltyrosine derivatives having common pharmacophores with beta-turn of neurotensin (NT(8-13)) and repeating the structure of a nonpeptide prototype, the atypical neuroleptic sulpiride. The aim of this study was to evaluate the effect of dilept on the level of spontaneous and K(+)-stimulated release of glutamate. The experiments were performed in vitro on the cortical brain slices of male Wistar rats. Dilept used in concentrations 10(-5) and 10(-6) mole/liter did not affect the spontaneous release of glutamate though markedly decreased the K(+)-stimulated release. A decrease in the glutamate release under the action of the neuroleptic could contribute to the neuroprotective activity of dilept.