ZTTA, a postproline cleaving enzyme inhibitor, improves cerebral ischemia-induced deficits in a three-panel runway task in rats

Pharmacology, Biochemistry, and Behavior
Y ShishidoS Watanabe

Abstract

We investigated the effect of N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA), a novel postproline cleaving enzyme (prolyl endopeptidase, PPCE) inhibitor, on the in vitro activity of rat brain PPCE and memory impairment induced by cerebral ischemia. ZTTA noncompetitively inhibited rat brain PPCE (ki = 2.9 microM). Cerebral ischemia for 5 min increased the number of errors in a working memory task with a three-panel runway paradigm. ZTTA at 6 mg/kg, administered immediately after blood flow reperfusion, significantly reduced the increase in working memory errors expected to occur 24 h after 5 min of ischemia. The antiamnesic action of ZTTA may be ascribable to a neuroprotective effect on the central nervous system due to some neuropeptides that are substrates of PPCE in the brain.

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Citations

Jul 8, 1999·European Journal of Pharmacology·Y ShishidoT Yokokura
Aug 26, 1999·Pharmacology, Biochemistry, and Behavior·S TanabeT Yokokura
Apr 14, 2011·Neuro-Signals·M José Moreno-BaylachJ Arturo García-Horsman
Apr 8, 2010·Journal of Neuroinflammation·Jofre Tenorio-LarangaJ Arturo García-Horsman
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Jan 12, 2010·Journal of Medicinal Chemistry·Janice LawandiNicolas Moitessier
Jun 30, 2021·Neurochemistry International·Ivan A LindhoutAndis Klegeris

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