Prolyl endopeptidase inhibitors

Prolyl endopeptidases hydrolyze proline-containing peptide hormones, several of which are implicated in learning and memory. 0N0-1603 (31) is a potent prolyl endopeptidase inhibitor (Ki = 12 nM) that reverses scopolamine-induced deficits in learning and memory in rats, restores decreased levels of choline and 5HT in aged rats and improves cognitive performance, and is also neuroprotective to CNS neurons undergoing apoptosis.44 While 0N0-1603 was advanced to phase II trials for senile dementia in Japan, it was discontinued in 1995.

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