Duloxetine increases the effects of levodopa in a rat model of Parkinson's disease

AbstractBackgroundIn patients with advanced Parkinson's disease, serotonergic and noradrenergic systems act as surrogates for the failing dopaminergic system. Treatment with a serotonin–noradrenaline reuptake inhibitor might help maintain levodopa‐derived dopamine levels in the dopamine‐denervated striatum. However, clinical utility of a serotonin–noradrenaline reuptake inhibitor for treatment of motor symptoms in Parkinson's disease is not yet clear.AimTo investigate whether pretreatment with duloxetine, one of the serotonin–noradrenaline reuptake inhibitors, has any impact on the effects of levodopa in a rat model of Parkinson's disease.MethodsWe used 6‐hydroxydopamine‐lesioned hemiparkinsonian rats. One group received duloxetine for 5 days and the other group received the same dose of saline. Levodopa was injected into each rat 6 h after the last administration of duloxetine or saline. An abnormal involuntary movement score was measured every 20 min during the 3‐h period after the injection of levodopa.ResultsLevodopa‐induced abnormal involuntary movement was significantly enhanced in duloxetine‐treated rats when compared with saline‐treated rats.ConclusionDuloxetine appears to increase the effects of levodopa in a rat model of Parkinson's disease, although it might increase the risk of levodopa‐induced dyskinesia.