Neurobehavioral Effects of N-phenylactyl-L-proglycine Ethyl Ester on Improving Cognition in Older Adults

Background: Much of current research focuses on diminishing the decline of cognition in older adults. Hypothesis: This study focuses on improving cognition in older adults, specifically using N-phenylactyl-L-prolylglycine ethyl ester (NPPEE), which is currently marketed in some countries to increase wakefulness. Materials and Methods: In a preliminary study, we tested this compound for its potential to promote wakefulness in young mice. Male Swiss-Webster mice were injected via the intraperitoneal route with varying doses of NPPEE ranging from 0.1 mg/kg to 4.0 mg/kg, using deionized water as the vehicle. Immediately after injection, the mice were placed into the locomotor activity study for 8 hours to test for stimulant and possible anxiolytic effect, as measured by their horizontal activity and center times, respectively. Results: In the first 10 minutes of the session, the mice injected with the NPPEE solution demonstrated significantly greater horizontal activity than those injected with deionized water only, but there was no effect on center time. This effect with horizontal activity was dose dependent, with 1 mg/kg having the maximum dose effect. These results suggest that NPPEE promotes wakefulness mildly. This effect was approximately 33% of the maximal stimulant effect of modafinil, which was tested as a standard. The next step is to examine the effects of NPPEE in mice on short term, working memory and cognitive flexibility using an active avoidance test. Conclusions: Thus far, the results suggest that this compound has potential as a psychogeriatric stimulant medication, and although the anxiolytic effect in the younger mice was not significant, other literature suggests that the effect is significant in older populations.