PT - JOURNAL ARTICLE AU - J. A. BEAVO AU - N. L. ROGERS AU - O. B. CROFFORD AU - J. G. HARDMAN AU - E. W. SUTHERLAND AU - E. V. NEWMAN TI - Effects of Xanthine Derivatives on Lipolysis and on Adenosine 3',5'-Monophosphate Phosphodiesterase Activity DP - 1970 Nov 01 TA - Molecular Pharmacology PG - 597--603 VI - 6 IP - 6 4099 - http://molpharm.aspetjournals.org/content/6/6/597.short 4100 - http://molpharm.aspetjournals.org/content/6/6/597.full SO - Mol Pharmacol1970 Nov 01; 6 AB - The lipolytic potencies of 64 compounds, mostly xanthine derivatives, were determined in epididymal fat cells. Nine of the compounds of widely varying lipolytic potency were examined as inhibitors of cyclic AMP phosphodiesterase activity. Substantial lipolytic effects were seen at concentrations producing less than 20% inhibition of phosphodiesterase activity. The most active compound, 1-methyl-3-isobutylxanthine, was about 15 times more potent than theophylline in both systems. Over a 20-fold range of concentrations, there was close agreement between the lipolytic activities of the compounds and their activities as inhibitors of phosphodiesterase. The close correlation between these two activities strongly indicates that the lipolytic activity of the xanthine derivatives is a result of inhibition of cyclic AMP phosphodiesterase. ACKNOWLEDGMENTS We are indebted to Dr. Donald E. Pearson, Professor of Chemistry, Vanderbilt University, for his helpful discussions. We also thank Drs. I. C. Winter, K. J. Rorig, and others of G. D. Searle and Company for the synthesis, purification, and gift of many of the test compounds.