EFFECT OF AIT-082, A PURINE ANALOG, ON WORKING-MEMORY IN NORMAL AND AGED MICE

Because working memory is the primary type of memory which is disrupted by Alzheimer's disease and stroke and during aging, any therapeutic drug for these conditions should improve and/or restore working memory. The win-shift memory paradigm has been shown to be an excellent model of working memory. In the present study, we examined the effects of a novel purine derivative, 4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid (AIT-082) and physostigmine (PHY) on working memory. Both AIT-082 and PHY improved memory in young mice and restored memory in mice with mild age-induced memory deficits; however only AIT-082 was also effective in subjects with moderate deficits. Neither drug improved memory in mice with severe memory deficits. AIT-082 exhibited effectiveness over a broad dose range (0.5-60 mg/ kg), and the effects lasted for seven days after a single high-dose drug administration. AIT-082 was devoid of any effects on performance variables and has not shown any toxic side effects, thus making it an interesting potential treatment for working memory deficits associated with aging, strokes, and Alzheimer's disease.