Riluzole prevents MPTP-induced parkinsonism in the rhesus monkey: a pilot study.
Previous studies have shown that riluzole (2-amino-6-trifluoromethoxy-benzothiazole), a drug which interferes with glutamate neurotransmission, has a neuroprotective action in rodent models of global and focal cerebral ischemia. In this pilot study, the protective and palliative effects of riluzole have been examined using an animal model of Parkinson's disease. Two monkeys were rendered hemiparkinsonian by one intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and motor signs were evaluated using clinical examination and electromyographic recordings. When riluzole (4 mg/kg) was administered before the injection of MPTP, parkinsonian motor symptoms, in particular bradykinesia and rigidity, were absent. When injected daily in one monkey which presented stable motor symptoms, bradykinesia and rigidity were significantly reduce d. Riluzole pretreatment induced a persistent increase in dopamine turnover when compared to MPTP alone. Thus, a possible neuroprotection and a facilitation of dopamine release may explain the behavioural effects reported with riluzole treatment. These preliminary results suggest that riluzole could possess neuroprotective and palliative effects in a primate model of Parkinson's disease.
Benazzouz
A
A
Laboratoire de Neurophysiologie, CNRS URA 1200, Université de Bordeaux 2, France.
Boraud
T
T
Dubédat
P
P
Boireau
A
A
Stutzmann
J M
JM
Gross
C
C
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D020267:MPTP Poisoning; D008253:Macaca mulatta; D009127:Muscle Rigidity / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000503:physiopathology / Q000517:prevention & control*; D010865:Pilot Projects; D019782:Riluzole; D015222:Sodium Channels / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*
D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D015222:Sodium Channels; D013844:Thiazoles; D019782:Riluzole; D004298:Dopamine