Doxofylline in rat brain in relation to locomotor activity

Doxofylline is a new xanthine derivative with significant bronchodilatatory activity. We have studied in HPLC the distribution of doxofylline in various areas of rat brain (cortex, cerebellum, limbic system) and its activity on the central nervous system by using a spontaneous motility test comparing it with aminophylline administered orally in equimolar doses (4.7 - 9.4 - 19 x 10(-5) mol/kg). Doxofylline is absorbed 3 or 4 times less than aminophylline at the same doses. Nevertheless, the quantity of doxofylline that goes to the brain is equivalent to that absorbed, whereas the quantity of aminophylline is about one-third. This is due to the greater liposolubility of doxofylline in comparison to aminophylline. In spite of the fact that doxofylline is easily distributed in the brain, spontaneous motility in animals is not modified, whereas aminophylline increases this activity significantly. The low affinity of doxofylline with adenosine receptors (A1 and A2) in comparison with aminophylline explains the lack of side effects on the central nervous system which has been amply documented for theophylline and for other methylxanthine derivatives.