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

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.
AuthorsY Shishido, M Furushiro, S Tanabe, S Nishiyama, S Hashimoto, M Ohno, T Yamamoto, S Watanabe
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 55 Issue 3 Pg. 333-8 (Nov 1996) ISSN: 0091-3057 [Print] UNITED STATES
PMID8951974 (Publication Type: Journal Article)
Chemical References
  • N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylacetal
  • Serine Proteinase Inhibitors
  • Thiazoles
  • Serine Endopeptidases
  • prolyl oligopeptidase
  • Animals
  • Brain (metabolism)
  • Brain Ischemia (physiopathology)
  • Conditioning, Operant (drug effects)
  • Male
  • Memory Disorders (prevention & control)
  • Memory, Short-Term (physiology)
  • Rats
  • Rats, Wistar
  • Serine Endopeptidases (metabolism)
  • Serine Proteinase Inhibitors (pharmacology)
  • Thiazoles (pharmacology)

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