Alzheimer's disease, cancer and the search for a better aspirin. Postgraduate course at Mount Sinai School of Medicine, New York, NY June 22-23, 2001.

The meeting was organized and chaired by Giulio Maria Pasinetti, Associate Professor of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. It was attended by ca. 150 physicians and basic medical scientists and consisted of 23 presentations on the effects of non-steroidal antiinflammatory drugs (NSAIDs), primarily cyclooxygenase 2 (COX-2) inhibitors, in Alzheimer’s disease (AD) and cancer. The meeting was supported by grants from Merck & Co. and Helsinn Healthcare. In his introductory remarks Pasinetti pointed out that there is substantial evidence that NSAIDs protect from colon cancer. They may also slow the progression of Alzheimer’s disease. He expressed hope that this meeting will provide an impetus for further evaluation and eventual use of NSAIDs in the therapy of these diseases. The first lecture, “Building a Better Aspirin, Experimental Approaches and Clinical Implications,” was delivered by D. L. DeWitt (Michigan State Univ., Lansing, MI, USA). He emphasized the importance of selective inhibition of COX-2 isoenzyme for side effect profile of inhibitors. Minor changes in the amino acid composition of COX-2, as compared to COX-1, increase the binding site pocket. Inhibitors with bulky side groups are more selective for COX-2 because they fit better to the larger binding site pocket. COX-2 inhibitors, unlike COX-1, do not require acidic side group for binding to the isoenzyme. The COX-2 + inhibitor complexes are not easily reversible, whereas binding of the inhibitors to COX-1 is freely reversible. There are also different modes of inhibition: time-dependent and competitive. Selective COX-2 inhibitors inhibit the isoenzyme time-dependently, the degree of inhibition increases with time. The same inhibitors may inhibit COX-1 competitively. At a low dose, aspirin is a selective COX-1 inhibitor. Among new COX-2 inhibitors valdeco-