Doxofylline, an antiasthmatic drug lacking affinity for adenosine receptors

In the present study the interaction of doxofylline, a new antiasthmatic drug, with A1- and A2-adenosine receptors of the guinea-pig brain and rat striatum was investigated in comparison with known methylxanthine derivatives. Inhibition studies of N6-cyclohexyl-3H-adenosine (3H-CHA), 1,3-diethyl-8-3H-phenylxanthine (3H-DPX) binding and 3H-5'-N-ethylcarboxamidoadenosine (3H-NECA) binding showed how doxofylline did not bind to adenosine receptors in a pharmacological fashion, since doxofylline affinity for A1- and A2-adenosine receptors lies in a 10(-4) M range, a concentration which is too high to have any pharmacological meaning or predictability. However, saturation binding studies demonstrate that doxofylline behaves as a competitive inhibitor of the 3 radioligands used to label adenosine receptors. These data seem to corroborate the theory that antagonism to adenosine receptors is not necessarily associated with bronchodilator activity of methylxanthines, and explain the lack of the typically unwanted side effects induced by methylxanthine derivatives after doxofylline administration.