ZTTA, A POSTPROLINE CLEAVING ENZYME-INHIBITOR, IMPROVES CEREBRAL ISCHEMIA-INDUCED DEFICITS IN A 3-PANEL RUNWAY TASK IN RATS

We investigated the effect of oxycarbonyl-thioprolyl-thioprolinal-dime thylacetal (ZTTA), a novel postproline cleaving enzyme (prolyl endopep tidase, PPCE) inhibitor, on the in vitro activity of rat brain PPCE an d memory impairment induced by cerebral ischemia. ZTTA noncompetitivel y inhibited rat brain PPCE (k(i) = 2.9 mu M). Cerebral ischemia for 5 min increased the number of errors in a working memory task with a thr ee-panel runway paradigm. ZTTA at 6 mg/kg, administered immediately af ter blood flow reperfusion, significantly reduced the increase in work ing memory errors expected to occur 24 h after 5 min of ischemia. The antiamnesic action of ZTTA may be ascribable to a neuroprotective effe ct on the central nervous system due to some neuropeptides that are su bstrates of PPCE in the brain. Copyright (C) 1996 Elsevier Science Inc .