Effects of the prolyl endopeptidase inhibitor S 17092 on cognitive deficits in chronic low dose MPTP-treated monkeys.

Abstract

A number of neuropeptides are affected in Parkinson's disease and the enzyme proline endopeptidase contributes to the degradation of many of these neuropeptides, some of which are linked to a variety of cognitive functions. In the present study, the effects of the highly potent proline endopeptidase inhibitor S 17092 on cognitive deficits in monkeys induced by chronic low dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were examined. Chronic low dose MPTP administration resulted in deficits in performance of variable delayed response, delayed matching-to-sample, and delayed alternation tasks. Seven day oral administration of S 17092 followed by single dose administration of the same dose on the day of testing significantly improved overall performance on these tasks. The most effective dose of S 17092 was 3 mg/kg. These results indicate that S 17092 has cognition-enhancing properties in this model of early parkinsonism.

• Authors: J S Schneider, M Giardiniere, P Morain
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 26 Issue 2 Pg. 176-82 (Feb 2002) ISSN: 0893-133X [Print] England
• PMID: 11790513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agents
• Indoles
• S 17092-1
• Serine Proteinase Inhibitors
• Thiazoles
• Thiazolidines
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Serine Endopeptidases
• Prolyl Oligopeptidases

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Animals
• Cognition Disorders (chemically induced, psychology)
• Conditioning, Operant (drug effects)
• Discrimination Learning (drug effects)
• Dopamine Agents
• Indoles (pharmacology)
• Macaca fascicularis
• Male
• Parkinson Disease, Secondary (chemically induced, psychology)
• Pattern Recognition, Visual (drug effects)
• Prolyl Oligopeptidases
• Psychomotor Performance (drug effects)
• Serine Endopeptidases (metabolism)
• Serine Proteinase Inhibitors (pharmacology)
• Thiazoles (pharmacology)
• Thiazolidines