Sensitivity of inbred mice to methylxanthines is not determined by plasma xanthine concentration.

Male CBA/J and SWR/J mice were tested with doses of caffeine, theophylline and 8-p-sulfophenyltheophylline (xanthine). Caffeine produced dose-related decreases in locomotor activity and colonic temperatures in SWR/J mice. However, caffeine produced increases in locomotor activity and failed to lower the body temperature of CBA/J mice. Theophylline produced a decrease in body temperature of SWR/J mice. Comparison of brain caffeine levels demonstrated no difference in brain pharmacokinetics. The peripherally active xanthine failed to alter body temperature at the same molar dose as that of theophylline. These data clearly demonstrate that genetic differences in the effects of methylxanthine are due to inherent differences in the central nervous system sensitivity of the two strains. The data further indicate that while differences in xanthine metabolism may occur in inbred mice, these differences are not a major factor in the acute, peak plasma level, effects of xanthines.