Dipyridamole in the treatment of schizophrenia: adenosine-dopamine receptor interactions

Objective: There is growing interest in investigating the adenosine-dopamin e interaction in the ventral striatum. Adenosine plays a role opposite to d opamine in the striatum and adenosine antagonists, like caffeine, produce s imilar effects to increased dopaminergic neurotransmission in the striatum. In particular, a strong antagonistic interaction between adenosine A(2A) a nd dopamine D-2 receptors takes place in the striopallidal GABAergic neuron es. Therefore, adenosine agonists or uptake inhibitors provide a potential new treatment for schizophrenia. We undertook a pilot trial to investigate whether the combination of haloperidol with dipyridamole, an uptake inhibit or of adenosine, was more effective than haloperidol alone. Methods: Thirty patients who met the DSM IV criteria for schizophrenia comp leted the study. Patients were allocated in a random fashion, 16 to haloper idol 20 mg/day plus dipyridamole 75 mg/day and 14 to haloperidol 20 mg/day plus placebo. Results: Although both protocols significantly decreased the score of the p ositive, negative and general psychopathological symptoms over the trial pe riod, the combination of haloperidol and dipyridamole was significantly bet ter than haloperidol alone in decreasing positive and general psychopatholo gy symptoms as well as PANSS total scores. Conclusion: Dipyridamole may be of therapeutic benefit in treating schizoph renia in combination with neuroleptics. However, a larger study to confirm our results is warranted.