The objective of this study is to evaluate the acute effects of a nonselective inhibitor of glutamate mediated synaptic transmission on the severity of parkinsonian signs and levodopa-associated motor response complications in patients with moderately advanced Parkinson's disease. In a controlled proof-of-principle clinical trial, the efficacy of the glutamate release inhibitor riluzole will be assessed through the use of validated motor function scales. Safety will be monitored by means of frequent clinical evaluations and laboratory tests.
INCLUSION CRITERIA: Males and females between the ages of 20-80 are eligible for study. Women must be either at least one year post-menopausal, or using an adequate contraceptive method for at least one month prior to and during participation in this study. All will carry the diagnosis of idiopathic Parkinson's disease based on the presence of a characteristic clinical history and neurological findings. All will have relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations. EXCLUSION CRITERIA: The presence or history of any medical condition that can reasonably be expected to subject the patient to unwarranted risk. Any clinically significant laboratory abnormalities including liver enzyme elevations more than two times the upper limit of normal, or neutropenia (wbc less than 3000). Parkinson's disease patients exhibiting diphasic or end-of dose dyskinesias or disabling dystonia will be excluded. Patients who are unable to be treated with levodopa/carbidopa alone or with a single, relatively short-acting dopamine agonist will also be excluded. Patients with a form of parkinsonism other than idiopathic PD or with a diagnosis of dementia (MMSE less than 24) or major psychiatric disorder (UPDRS [Part I Item 3] greater than or equal to 2). Patients with unacceptable prior/concomitant medications will also be excluded. Since the influence of any investigational compound on the unborn child and reproductive organs is unknown, pregnant women and those not practicing effective means of birth control will be excluded as well. Patients with prior bilateral surgical intervention for the treatment of parkinsonian symptoms, i.e. deep brain stimulation, pallidotomy, fetal tissue transplantation as well as patients must at risk for hypotension, cardiac arrhythmia, and/or myocardial ischemia secondary to intravenous levodopa challenge will be excluded.