The effects of a competitive prolyl endopeptidase inhibitor benzyloxycarbonyl-alanyl-proline were studied in rats with experimental dopamine deficiency-dependent depressive syndrome due to systemic administration of a proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 14 days. The inhibitor was injected intraperitoneally 30 min before treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2nd week of the study). This substance contributed to rapid disappearance of depressive symptoms during the recovery of behavioral activity. Our results indicate that benzyloxycarbonyl-alanyl-proline has the antidepressant properties.
Title: Behavioral changes in rats induced by a dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyanopyrrolidine: experimental model of anxiety-depression disorder Krupina NA, Kushnareva EY, Khlebnikova NN, Zolotov NN, Kryzhanovskii GN Ref: Bulletin of Experimental Biology & Medicine, 147:285, 2009 : PubMed
Administration of a synthetic dipeptidyl peptidase IV inhibitor methionyl-2(S)-cyanopyrrolidine (1 mg/kg) to rats during the early postnatal period was followed by the development of behavioral changes in young and adult animals. The degree of anxiety in the elevated plus maze increased in treated rats at the age of 1-2 months. Depressive behavior in the forced swimming test was typical of animals aging 2-3 months. Diazepam reduced the severity of anxiety in treated rats. Melipramine had a normalizing effect on swimming behavior. A novel prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine had the antidepressant properties.
