30:718:409 Lecture 34: CNS Stimulants Part 1 (Dr. Hu)

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For cns stimulation, we want to increase the concentration of these in the brain. The general structure of xanthine [3,7-dihydro-1h-purine-2,6-dione] is shown below: Same numbering and structure as purine, with added oxo groups at 2 and 6. But hard to tell the moa (because not powerful enough) The naturally occurring methylxanthines are caffeine, theophylline, and theobromine. The methylxanthines exert their effects by several mechanisms: Competetively blocking adenosine receptors (antagonizes a1 receptors) probably most important (note: the methylxanthines resemble adenosine to a certain extent) Levels of caffeine in different foods (highest in drip coffee, less in tea, then cocoa, but soda is up there) Common with all compounds, they undergo alkylation to result in mono/dimethyl metabolites. Never get fully demethylated, and not entirely oxidized, so produce uric acid. Want to avoid that (lactim form is the one that becomes ionized) Uric acid has a pka of 5. 4 (caffeine cannot be acidic, but theophylline and aminophylline can)

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