Adenosine antagonist properties of carbamazepine.

Abstract

The binding of adenosine agonists and antagonists to the adenosine receptor is differentially affected by both temperature and guanine nucleotides. Agonist binding is facilitated at higher temperatures; the reverse is true for adenosine antagonists. In the present study, we demonstrate the feasibility of utilizing the temperature dependency of agonist/antagonist binding to the adenosine receptor in binding inhibition studies. We show that the anticonvulsant drug carbamazepine (CBZ) and several of its structural analogs behave in a manner identical to that of a series of adenosine antagonists; i.e., they are more potent inhibitors of [3H]cyclohexyladenosine (CHA) binding at 8 degrees C as compared to 37 degrees C and are equipotent as inhibitors of [3H]diethylphenylxanthine (DPX) binding at 0 and 30 degrees. We also show that the potency of CBZ and derivatives as inhibitors of [3H]CHA binding is markedly increased in the presence of 10 microM GppNHp, whereas their potency as inhibitors of [3H]DPX binding is unaffected by this guanine nucleotide. These data in conjunction with past studies support the hypothesis that CBZ and its derivatives act as adenosine antagonists at the level of binding interactions at the adenosine receptor.