PROPRANOLOL significantly reduces Parkinson’s disease (PD) tremor and inhibits tremor-related activity in the motor cortex, independent of stress levels, new research has found.
Parkinson’s disease tremor is believed to originate in the basal ganglia and be amplified by the cerebello-thalamo-cortical circuit. As stress exacerbates tremor, the noradrenergic system may play a role in this amplification. This study aimed to determine whether propranolol, a non-selective beta-adrenergic receptor antagonist, reduces PD tremor and whether this effect is specific to stressful conditions.
A placebo-controlled, double-blind crossover study was conducted with 27 PD patients experiencing prominent resting tremor. Participants received a single 40 mg dose of propranolol or placebo on separate days in a counterbalanced order. Tremor severity was measured using accelerometry, and tremor-related brain activity was assessed via functional magnetic resonance imaging (fMRI). Heart rate and pupil diameter were also monitored. To examine stress effects, participants engaged in a cognitive load task linked to noradrenergic activity. Results showed that tremor power increased significantly during cognitive load compared to rest (F[1,19] = 13.8; p = 0.001; η² = 0.42), confirming stress-related tremor exacerbation. Propranolol reduced tremor power relative to placebo (F[1,19] = 6.4; p = 0.02; η² = 0.25), with no significant interaction between drug and stress conditions. fMRI data revealed that propranolol significantly reduced tremor-related activity in the motor cortex (F[1,21] = 5.3; p = 0.03; η² = 0.20), suggesting a direct cortical mechanism of action.
These findings suggest that propranolol effectively reduces PD tremor across both stressful and resting conditions, likely by modulating activity in the motor cortex. Clinically, propranolol presents a viable treatment for PD tremor beyond its traditional use in essential tremor, providing an option for patients whose symptoms are exacerbated by stress. Future research should explore the role of beta-1 receptors in mediating this effect, as more targeted interventions could offer similar benefits with fewer side effects. Additionally, given the known long-term neuroplastic effects of noradrenaline on the motor cortex, sustained propranolol use may confer lasting improvements in tremor control, warranting further investigation into its chronic administration in PD management.
Katrina Thornber, EMJ
Reference
van der Heide A et al. Propranolol reduces parkinson’s tremor and inhibits tremor-related activity in the motor cortex: a placebo-controlled crossover trial. Ann Neurol. 2024;DOI:10.1002/ana.27159.
