Lisuride Patch to Treat Parkinson's Disease

* INCLUSION CRITERIA: Individuals who meet all of the following inclusion criteria will be eligible to participate: Patient has been diagnosed with idiopathic Parkinson's disease. Patient has relatively advanced disease with levodopa-associated motor response complications, including, peak-dose dyskinesias and wearing-off fluctuations. Patient can be optimized on oral levodopa, usually with an interdose interval of less than or equal to 3.0 hours. Patient is willing to adhere to protocol requirements as evidenced by written, informed consent. Patient is between the ages of 40 and 80 years, inclusive. EXCLUSION CRITERIA: Individuals meeting any of the following exclusion criteria immediately before or during the study will not be enrolled or will be immediately excluded from the study, as appropriate: Patient has a history of any medical condition that can reasonably be expected to subject them to unwarranted risk, such as history of severe cardiac (myocardial infarction within 12 months prior to study, dysrhythmia), severe cerebrovascular, convulsive, significant hepatic (enzyme elevation greater than twice the upper limit of normal), or renal (creatinine exceeding the upper limit of normal) disorder. Patient is taking a prohibited medication. Patient is unable to be treated with levodopa/carbidopa alone while a participant in this protocol. Patient has unilateral or bilateral deep brain stimulating (DBS) devices who are unable or unwilling to turn them off during the period of protocol participation. Patient has prior bilateral pallidotomy. Patient has cognitive impairment as indicated by a Minimental status examination (MMSE) score less than 25. Patient has not been using an adequate contraceptive method for the last 2 months, or (if female) is pregnant or breastfeeding, or not at least one year post-menopausal or unwilling or unable to continue contraceptive use during the study. Patient has participated in a clinical study with an investigational drug within the last 30 days. Patient has dermatological problems, such as eczema or hirsutism, that would interfere with transcutaneous therapy. Patients with known hypersensitivity to lisuride or to skin patch materials. Patients with slow lisuride metabolism due to CYP450 2D6 deficiency or requiring drugs also metabolized by CYP450 2D6, including Beta-blockers: S-metoprolol, propafenone, antidepressants: amitriptyline, clomipramine, desipramine, imipramine, antipsychotics: haloperidol, risperidone, thioridazine, other drug: codeine, dextromethorphan, flecainide, ondansetron, and tramadol. CONCOMITANT MEDICATION EXCLUSION: The following medications are prohibited for at least one month prior to randomization (except as noted below) and during the course of study: Dopamine agonists of any kind (for 1 week, Cabergoline for 8 weeks). Any investigational drug not specifically permitted in the protocol. MAO inhibitors, such as selegiline (for 2 months). Anticholinergics. Drugs not used primarily to treat Parkinson's disease but which may modify parkinsonian symptoms, including neuroleptics, metoclopramide and alpha or beta adrenergic receptor antagonists. Drugs considered to ameliorate dyskinesias including NMDA antagonists (such as amantadine, budipine, memantine, remacemide and dextromethorphan), alpha or beta adrenergic receptor antagonists, anxiolytics (such as buspirone) with the exception of antidepressants from the SSRI group such as fluoxetine, antipsychotics (such as clozapine, quetiapine and olanzapine), cannabinoid receptor antagonists, and adenosine A2a antagonists, or to exacerbate dyskinesias (such as sodium valproate and CNS stimulants). Drugs known to have 5HT receptor subtype affinity (such as ritanserin, sumatriptan).