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Famotidine, a Histamine H 2 Receptor Antagonist, Does Not Reduce Levodopa‐Induced Dyskinesia in Parkinson's Disease: A Proof‐of‐Concept Study
Author(s) -
Mestre Tiago A.,
Shah Binit B.,
Connolly Barbara S.,
Aquino Camila,
Al Dhakeel Amaal,
Walsh Richard,
Ghate Taneera,
Lui Jane P.,
Fox Susan H.
Publication year - 2014
Publication title -
movement disorders clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 18
ISSN - 2330-1619
DOI - 10.1002/mdc3.12061
Subject(s) - famotidine , dyskinesia , antagonist , levodopa , parkinson's disease , histamine , medicine , pharmacology , psychology , disease , receptor
The neural mechanisms underlying levodopa‐induced dyskinesia ( LID ) in Parkinson's disease ( PD ) may involve histamine (H 2 ) receptors on striatopallidal pathways. We recently demonstrated that the clinically available oral histamine H 2 receptor antagonist (H 2 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 ( UD ys RS ; part III ) between placebo and famotidine. Secondary outcomes were UD ys RS (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 ( AE s). 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 AE s. 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.