The National Institute on Aging (part of the National Institutes of Health) and Axonyx are investigating phenserine, a phenylcarbamate derivative of physostigmine, as a potential therapy for Alzheimer's disease (AD). The first phase I trial has been completed and, pending the results of a second phase Ib multiple dose study, a phase II efficacy study is scheduled for the fourth quarter of 2000 with completion expected during 2001. Axonyx filed an IND in 1998, which was approved in November 1999, and the company began phase I trials in December 1999 in the US. A second phase I trial, in a group of healthy, elderly volunteers, was initiated in February 2000. Phenserine reduces the production of the amyloid precursor protein and beta-amyloid in vitro. When added to human neuronal cells, Phenserine decreased the production of beta-amyloid peptide by 30%. Phenserine also showed small, non dose-dependent effects on learning in studies in aged rats and lower toxicity than physostigmine. Phenserine has a long duration of action (t(1/2) = 8 to 10 h).