[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.
Us
K S
KS
Klodt
P M
PM
Kudrin
V S
VS
Arkhipenko
N V
NV
Gudasheva
T A
TA
Ostrovskaia
R U
RU
D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D009496:Neurotensin / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D014150:Antipsychotic Agents; C401484:GZR 123; D018696:Neuroprotective Agents; D009496:Neurotensin; D018698:Glutamic Acid; D014443:Tyrosine; D011392:Proline