Improving effects of Z-321, a new prolyl endopeptidase inhibitor, on the impaired cerebral functions

We investigated profile of Z-321, a new prolyl endopeptidase(PEP) inhibitor, for an enhancer of cerebral functions. Z-321 competitively and reversibly inhibited degradation of proline-containing neuropeptides such as Arg-vasopressin by PEP from canine brain Ki=6nM for Arg-vasopressin ) . The inhibit...

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Published in:Japanese Journal of Pharmacology 1996, Vol.71 (suppl.2), p.279-279
Main Authors: Yoshiaki Tanaka, Koji Yoshinaga, Kunie Kizaki, Hiroyasu Furuichi, Naoki Nakata, Junkichi Izumi, Naoyoshi Miura, Toshihiro Matsumura, Masataka Washizuka, Yu Kuwabara, Yugo Ikeda
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Language:Japanese
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Summary:We investigated profile of Z-321, a new prolyl endopeptidase(PEP) inhibitor, for an enhancer of cerebral functions. Z-321 competitively and reversibly inhibited degradation of proline-containing neuropeptides such as Arg-vasopressin by PEP from canine brain Ki=6nM for Arg-vasopressin ) . The inhibition was highly specific to PEP. Oral administration of Z-321 to mice or rats dose-dependently inhibited PEP in the brain, indicating the penetration of the drug into the brain. Z-321(p.o.) prolonged survival time in hypoxic mice. The drug(p.o.) ameliorated behavioral impairment of rats induced by CO_2 or electroconvulsive shock in step-through passive avoidance tasks. In mice the drug(p.o.) improved impaired step-down passive avoidance response induced by cerebral ischemia. These results suggest that Z-321 may provide a therapeutic tool for the cerebral dysfunctions observed in Alzheimers disease and cerebrovascular disease.
ISSN:0021-5198