(2s-3as-7as)-1-(((r-r)-2-phenylcyclopropyl)carbonyl)-2-((thiazolidin-3-yl)carbonyl)octahydro-1h-indole and Parkinson-Disease--Secondary

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.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Cognition Disorders; Conditioning, Operant; Discrimination Learning; Dopamine Agents; Indoles; Macaca fascicularis; Male; Parkinson Disease, Secondary; Pattern Recognition, Visual; Prolyl Oligopeptidases; Psychomotor Performance; Serine Endopeptidases; Serine Proteinase Inhibitors; Thiazoles; Thiazolidines