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. 2014 Jun 26;1(3):219-224.
doi: 10.1002/mdc3.12061. eCollection 2014 Sep.

Famotidine, a Histamine H2 Receptor Antagonist, Does Not Reduce Levodopa-Induced Dyskinesia in Parkinson's Disease: A Proof-of-Concept Study

Tiago A Mestre  1 , Binit B Shah  2 , Barbara S Connolly  3 , Camila de Aquino  4 , Amaal Al Dhakeel  4 , Richard Walsh  5 , Taneera Ghate  4 , Jane P Lui  6 , Susan H Fox  4
Affiliations

Famotidine, a Histamine H2 Receptor Antagonist, Does Not Reduce Levodopa-Induced Dyskinesia in Parkinson's Disease: A Proof-of-Concept Study

Tiago A Mestre et al. Mov Disord Clin Pract. .

Abstract

The neural mechanisms underlying levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) may involve histamine (H2) receptors on striatopallidal pathways. We recently demonstrated that the clinically available oral histamine H2 receptor antagonist (H2 RA), famotidine, can reduce l-dopa-induced chorea in MPTP-lesioned macaques. We hypothesized that famotidine may be useful in the treatment of LID in PD patients. We performed a proof-of-concept, double-blind, randomized, multiple cross-over (4×) trial. Seven PD subjects with bothersome dyskinesia were randomized to oral famotidine 80, 120, and 160 mg/day and placebo. Each subject was randomized to receive each of the four treatment phases for 14 days followed by a 7-day wash-out period between each treatment phase. The primary outcome measure was change in the Unified Dyskinesia Rating Scale (UDysRS; part III) between placebo and famotidine. Secondary outcomes were UDysRS (parts I and II), Global Impression of Change, Lang-Fahn Activities of Daily Living Dyskinesia Scale, Unified Parkinson's Disease Rating part III, and adverse events (AEs). Outcomes were evaluated pre- and post-treatment per dose and analyzed using a mixed-effects linear model. There was no significant effect of famotidine treatment on any of the primary or secondary outcome measures compared to placebo (each dose and all doses combined). There were no significant AEs. Even though the sample size of the current study is limited, famotidine seems to be safe in patients with PD and LID, but showed no potential as an antidyskinetic agent.

Keywords: H2 antagonist; Parkinson's disease; dyskinesia; famotidine; histamine.

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Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Change in UDysRS part III (Impairment) (yy axis) at each treatment period (xx axis) from start to end of treatment. Negative values represent improvement. Difference between different treatment doses and placebo (treatment = 0).
See this image and copyright information in PMC

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