title: Effect of prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine on activity of proline-specific peptidases in brain structures of rats with experimental MPTP-induced depressive syndrome.
abstract: A noncompetitive synthetic inhibitor of prolyl endopeptidase benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine (1.0 mg/kg intraperitoneally for 2 weeks) prevented the increase in activity of prolyl endopeptidase in the frontal cortex, striatum, and hypothalamus and activation of dipeptidyl peptidase IV in the frontal cortex of rats with experimental dopamine deficiency-dependent depressive syndrome caused by administration of proneurotoxin MPTP (2 weeks). Our results suggest that the antidepressive effect of prolyl endopeptidase inhibitor is at least partly related to prevention of enzyme activation in the frontal cortex. The antistress effect of this substance can be associated with prevention of enzyme activation in the hypothalamus.
authors.affiliation: Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences; Laboratory of Psychopharmacology, V. V. Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia. nanikh@yandex.ru. N. N. Khlebnikova.
authors.forename: N N
authors.initials: NN
authors.lastname: Khlebnikova
authors.forename: N A
authors.initials: NA
authors.lastname: Krupina
authors.forename: N G
authors.initials: NG
authors.lastname: Bogdanova
authors.forename: N N
authors.initials: NN
authors.lastname: Zolotov
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D007274:Injections, Intraperitoneal; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000008:administration & dosage; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D011480:Protease Inhibitors; D011759:Pyrrolidines; C543067:benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008715:Methionine; D018819:Dipeptidyl Peptidase 4; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases