Alkylxanthines: inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of brain phosphodiesterase activity. |
| |
| Authors: | F W Smellie C W Davis J W Daly J N Wells |
| |
| Institution: | 1. Laboratory of Bioorganic Chemistry National Institute of Arthritis, Metabolism, and Digestive Diseases National Institutes of Health Bethesda, Maryland 20205, USA;1. Department of Pharmacology Vanderbilt University Nashville, Tennessee 37231, USA |
| |
| Abstract: | A series of 1, 3-dialkylxanthines was examined as antagonists of adenosine-induced accumulation of cyclic AMP in guinea pig cerebral cortical slices and as inhibitors of brain phosphodiesterases. The order of potency as adenosine-antagonists was: 8-phenyltheophylline (IC50 6 μM) > 1, 3-dibutylxanthine (IC50 30 μM), 1, 3-dipropylxanthine > theophylline (IC50 60 μM), 3-isobutyl-1-methylxanthine (IBMX), 1, 3, 7-triethylxanthine > 7-benzyl IBMX (IC50 100 μM), 8-methyl IBMX > 7-benzyl-8-bromo IBMX, 9-methyl IBMX, 8-bromo IBMX, 1-isoamyl-3-isobutylxanthine. The order of potency as inhibitors of brain calcium-dependent phosphodiesterase was: 7-benzyl IBMX (IC50 1.5 μM), 7-benzyl-8-bromo IBMX > 8-methyl IBMX (IC50 4.5 μM) > IBMX (IC50 7.5 μM), 8-bromo IBMX > 9-methyl IBMX (IC50 40 μM), 1, 3, 7-triethylxanthine > 1, 3-dibutylxanthine (IC50 100 μM), 1-isoamyl-3-isobutylxanthine > theophylline. 8-Phenyltheophylline and 1, 3-dibutylxanthine represented potent adenosine-antagonists with relatively low activity as phosphodiesterase inhibitors whereas 7-benzyl IBMX and 7-benzyl-8-bromo-IBMX were potent inhibitors of the calcium-dependent phosphodiesterase with relatively low activity as adenosine-antagonists. None of the compounds were potent inhibitors of the brain calcium-independent phosphodiesterase, although 1-isoamyl-3-isobutylxanthine might prove useful as an inhibitor of this enzyme because of its very low activity as an adenosine-antagonist. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
