Analgesic effect of caffeine and clomipramine: a possible interaction between adenosine and serotonin systems

The goals of this study were to determine whether the nonselective adenosine receptor antagonist caffeine exerts an analgesic effect and to investigate the time-dependent influence of the selective serotonin reuptake inhibitor clomipramine on the action of caffeine. Results suggest a possible interaction between serotonin and adenosine systems, which may contribute to the analgesic action of drugs. Therefore, the hot-plate and formalin tests were employed in order to measure the response to painful thermic and chemical stimuli. Results have shown that caffeine (1.67, 16.7 and 67 mg kg(-1), i.p.) exerts a direct dose-dependent analgesic action. When caffeine (1.67 and 16.7 mg kg(-1)) was combined with clomipramine (3 mg kg(-1) i.p.), an enhanced analgesic effect was obtained. However, the same combinations were ineffective in a subacute model. In this model, clomipramine was administered for 14 days and the respective dose of caffeine was added on the last day. Therefore, it can be concluded that the serotonin system interacts with the analgesic action of caffeine and that a long-term use of clomipramine probably triggers subsensitivity of adenosine receptors.