Doxofylline

The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation.

The interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking. Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed. Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation.

There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study. It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro.Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells.