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

• Published in: Neurology Vol. 56; no. 4; pp. 455 - 462
• Main Authors: Shoulson, I, Penney, J, McDermott, M, Schwid, S, Kayson, E, Chase, T, Fahn, S, Greenamyre, J T, Lang, A, Siderowf, A, Pearson, N, Harrison, M, Rost, E, Colcher, A, Lloyd, M, Matthews, M, Pahwa, R, McGuire, D, Lew, M F, Schuman, S, Marek, K, Broshjeit, S, Factor, S, Brown, D, Feigin, A, Mazurkiewicz, J, Ford, B, Jennings, D, Dilllon, S, Comella, C, Blasucci, L, Janko, K, Shulman, L, Wiener, W, Bateman-Rodriguez, D, Carrion, A, Suchowersky, O, Lafontaine, A L, Pantella, C, Siemers, E, Belden, J, Davies, R, Lannon, M, Grimes, D, Gray, P, Martin, W, Kennedy, L, Adler, C, Newman, S, Hammerstad, J, Stone, C, Lewitt, P, Bardram, K, Mistura, K, Miyasaki, J, Johnston, L, Cha, J H, Tennis, M, Panniset, M, Hall, J, Tetrud, J, Friedlander, J, Hauser, R, Gauger, L, Rodnitzky, R, Deleo, A, Dobson, J, Seeberger, L, Dingmann, C, Tarsy, D, Ryan, P, Elmer, L, Ruzicka, D, Stacy, M, Brewer, M, Locke, B, Baker, D, Casaceli, C, Day, D, Florack, M, Hodgeman, K, Laroia, N, Nobel, R, Orme, C, Rexo, L, Rothenburgh, K, Sulimowicz, K, Watts, A, Wratni, E, Tariot, P, Cox, C, Leventhal, C, Alderfer, V, Craun, A M, Frey, J, McCree, L, McDermott, J, Cooper, J, Holdich, T, Read, B
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 27-02-2001
• Subjects: Acetamides - adverse effects; Acetamides - therapeutic use; Aged; Biological and medical sciences; Double-Blind Method; Drug toxicity and drugs side effects treatment; Female; Humans; Male; Medical sciences; Middle Aged; Multicenter Studies as Topic; Parkinson Disease - drug therapy; Patient Compliance; Pharmacology. Drug treatments; Receptors, Glutamate; Toxicity: nervous system and muscle; Human; Nervous system diseases; Toxicity; Multicenter study; Adjuvant treatment; Parkinson disease; Glutamate receptor; Antiparkinson agent; Cerebral disorder; Involuntary movement; Dose activity relation; Chemotherapy; Randomization; Remacemide; Central nervous system disease; Double blind study; Adult; Degenerative disease; Antagonist; Levodopa; Neurological disorder; Extrapyramidal syndrome; Dyskinesia
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.56.4.455

Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa.
In a multicenter, randomized, double-blind, placebo-controlled, parallel-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 objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy.
Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant.
Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.