PROTECTIVE EFFECT OF EURYSTATIN-A AND EURYSTATIN-B, NEW PROLYL ENDOPEPTIDASE INHIBITORS, ON SCOPOLAMINE-INDUCED AMNESIA IN RATS

Eurystatins A and B, which are produced by Streptomyces eurythermus R353-2 1, potently inhibited Flavobacterium prolyl endopeptidase (PED) with IC50 values of 0.004 and 0.002 mug/ml, respectively, while no inhibition was observed against another 5 proteases, even at 100 mug/ml. The protective effect of eurystatins A and B against scopolamine (3 mg/kg, i.p.)-induced amnesia in rats was evaluated by the step-through one-trial passive avoidance method. When administered i.p. 30 min prior to the acquisition trial, both eurystatins A, at 2 - 8 mg/kg, and B, at 4 - 8 mg/kg, significantly protected rats from the amnesic effect of scopolamine without behavioral side effects.