Levodopa Impairs the Energy Metabolism of the Basal Ganglia In Vivo

Abstract

ObjectiveOne proposed mechanism of disease progression in Parkinson's disease includes the interplay of endogenous dopamine toxicity and mitochondrial dysfunction. However, the in‐vivo effects of exogenous dopamine administration on cerebral bioenergetics are unknown.MethodsWe performed a double‐blinded, cross‐over, placebo‐controlled trial. Participants received either 200/50 mg levodopa/benserazide or a placebo and vice versa on the second study visit. Clinical assessments and multimodal neuroimaging were performed, including 31phosphorus magnetic resonance spectroscopy of the basal ganglia and the midbrain.ResultsIn total, 20 (6 female) patients with Parkinson's disease and 22 sex‐ and age‐matched healthy controls (10 female) were enrolled. Treatment with levodopa/benserazide but not with placebo resulted in a substantial reduction of high‐energy phosphorus‐containing metabolites in the basal ganglia (patients with Parkinson's disease: −40%; healthy controls: −39%) but not in the midbrain. There were no differences in high‐energy phosphorus‐containing metabolites for patients with Parkinson's disease compared to healthy controls in the OFF state and treatment response.InterpretationExogenously administered levodopa/benserazide strongly interferes with basal ganglia high‐energy phosphorus‐containing metabolite levels in both groups. The lack of effects on midbrain levels suggests that the observed changes are limited to the site of dopamine action. ANN NEUROL 2024;95:849–857