Interactions of the anticonvulsant carbamazepine with adenosine receptors. 2. Pharmacological studies

The interactions of carbamazepine with adenosine receptors were studied in two pharmacological systems. In the isolated guinea pig ileum, several adenosine agonists and carbamazepine potently inhibited nicotine-stimulated and electrically stimulated contractions in a manner sensitive to the adenosine antagonist theophylline. High concentrations of carbamazepine were able to reduce the inhibition of electrically stimulated contractions by the adenosine agonist l-methylisoguanosine. The ability of theophylline to reduce the anticonvulsant efficacy of several drugs against pentylenetetrazole-induced seizures in mice was investigated. Theophylline pretreatment failed to alter anticonvulsant protection by trimethadione and sodium valproate, but significantly decreased the anticonvulsant effects of carbamazepine and phenobarbital. These results suggest that carbamazepine may exert some of its anti-convulsant effects by acting as a partial agonist at adenosine receptors.