Effects of the prolyl endopeptidase inhibitor S 17092 on cognitive deficits in chronic low dose MPTP-treated monkeys.
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.
Schneider
J S
JS
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA. jay.schneider@mail.tju.edu
Giardiniere
M
M
Morain
P
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D015259:Dopamine Agents; D007211:Indoles / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000523:psychology; D010364:Pattern Recognition, Visual / Q000187:drug effects; D000085822:Prolyl Oligopeptidases; D011597:Psychomotor Performance / Q000187:drug effects; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D015259:Dopamine Agents; D007211:Indoles; C118986:S 17092-1; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; D053778:Thiazolidines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases