Introduction: Some alpha-1-adrenergic receptor antagonists (AARA), such as terazosin, stimulate glycolysis and increase cellular ATP levels through activation of phosphoglycerate kinase (PGK1), which has been theorized to be of therapeutic benefit in patients with Parkinson’s disease (PD).

Research Question or Hypothesis: What is the effect of AARA on PD related symptoms?

Study Design: Retrospective Cohort

Methods: Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000-2019 and were concurrently prescribed an AARA. The count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK activating AARA versus tamsulosin, using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, non-motor symptoms, and other potential complications as clinical markers for the progression of PD.

Results: A total of 127,142 patients initiated drug therapy for PD during the observation period, of which 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n=14,571) than tamsulosin (n=9,968) (IRR=0.80; 95% CI: 0.77-0.83), which remained significant after adjustment for confounding factors (IRR=0.85; 95% CI: 0.81-0.88) and in sensitivity analyses.

Conclusion: Patients prescribed a PGK1 activating AARA had fewer PD-related outcome events compared to patients prescribed tamsulosin. These results may indicate a future role for terazosin and other PGK1 activators in slowing disease progression of PD, however future randomized controlled trials are needed to fully assess this relationship.