A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease

Background: Preclinical studies suggest that glutamate antagonists help ame liorate motor fluctuations in patients with PD treated with levodopa. Metho ds: In a multicenter, randomized, double-blind, placebo-controlled, paralle l-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary ob jective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monit ored with home diaries and the Unified PD Rating Scale (UPDRS) to collect p reliminary data on treatment efficacy. Results: Remacemide was well tolerat ed up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a f our times daily schedule. The most common dosage-related adverse events wer e dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement i n the patients treated with 150 and 300 mg/d remacemide compared with place bo-treated patients, although these improvements were not significant. Conc lusion: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limite d power to detect therapeutic effects, the observed improvement is consiste nt with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrah ydropyridine-induced parkinsonian signs and symptoms. Additional studies ar e warranted to confirm these results over an extended period of observation , and to explore the potential neuroprotective effects of remacemide in slo wing the progression of PD.