tolcapone and ropinirole

The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Non- efficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.

Topics: Amantadine; Antiparkinson Agents; Apomorphine; Benzophenones; Benzothiazoles; Bromocriptine; Cabergoline; Catechol O-Methyltransferase Inhibitors; Deep Brain Stimulation; Dihydroergocryptine; Ergolines; Fetal Tissue Transplantation; Globus Pallidus; Humans; Indans; Indoles; Levodopa; Lisuride; Mesencephalon; Monoamine Oxidase Inhibitors; Neurosurgical Procedures; Nitrophenols; Parkinson Disease; Pergolide; Piribedil; Pramipexole; Selegiline; Thiazoles; Tolcapone

Topics: Amantadine; Benzophenones; Benzothiazoles; Brain Injuries; Catechols; Dopamine Agents; Humans; Indoles; Neuroprotective Agents; Nitriles; Nitrophenols; Patient Selection; Pramipexole; Selegiline; Thiazoles; Tolcapone

Since the introduction of levodopa to treat Parkinson's disease (PD), several new therapies have been directed at improving symptom control, which can decline after a few years of levodopa therapy. Dopaminergic agents can serve as adjuncts or as alternatives to levodopa. In addition, a new class of drugs, catechol-O-methyltransferase inhibitors, can extend the duration of levodopa action. Although surgical options such as pallidotomy offer improvement of parkinsonism beyond the realm of pharmacologic treatment, judicious administration of drugs in combination can generally solve most problems of PD.

Topics: Antiparkinson Agents; Benzophenones; Benzothiazoles; Cabergoline; Catechol O-Methyltransferase Inhibitors; Dopamine Agonists; Drug Synergism; Enzyme Inhibitors; Ergolines; Humans; Indoles; Levodopa; Nitrophenols; Parkinson Disease; Pramipexole; Thiazoles; Tolcapone

To summarize the development, pharmacology, pharmacokinetics, efficacy, and safety of five investigational antiparkinsonian drugs that are in or have recently completed Phase III trials: three dopamine agonists, pramipexole, ropinirole, and cabergoline; and two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone. The pathophysiology and the role of dopamine in Parkinson's disease are also reviewed.. A MEDLINE search of relevant English-language literature, clinical studies, abstracts, and review articles pertaining to Parkinson's disease was conducted. Manual searches of 1996/1997 meeting abstracts published by the American Academy of Neurology and the Movement Disorders Society were also performed. Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic data.. Clinical trial investigations selected for inclusion were limited to human subjects. Interim analyses after 6 months for long-term clinical studies in progress were included. Pharmacokinetic data from animals were cited if human data were unavailable. Statistical analyses for all studies were evaluated.. By selectivity targeting D2 receptors, the newer dopamine agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the introduction of levodopa and thus the occurrence of levodopa-induced dyskinesias. In addition, they are efficacious as adjunctive therapies in patients with advanced Parkinson's disease. Unlike the currently available dopamine agonists, pramipexole and ropinirole are non-ergot derivatives and do not cause skin inflammation, paresthesias, pulmonary infiltrates, or pleural effusion. The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson's disease.. Interim 6-month analyses of pramipexole, ropinirole, and cabergoline for symptomatic treatment of early Parkinson's disease have shown these drugs to be efficacious and relatively well-tolerated when used as monotherapy. Their role in delaying the development of motor fluctuations and delaying the addition of levodopa is the subject of long-term clinical studies. In advanced stages of Parkinson's disease, these medications were also efficacious; however, the main adverse effects included dyskinesias, somnolence, and hallucinations. The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone has also demonstrated efficacy in patients with motor fluctuations. Both drugs are relatively well-tolerated, with the exception of dyskinesias that require reduction of the levodopa dosage and occasional diarrhea.

Topics: Benzophenones; Benzothiazoles; Cabergoline; Catechol O-Methyltransferase Inhibitors; Catechols; Dopamine Agonists; Enzyme Inhibitors; Ergolines; Humans; Indoles; Nitriles; Nitrophenols; Parkinson Disease; Pramipexole; Receptors, Dopamine D2; Thiazoles; Tolcapone

New medications recently developed for treating Parkinson's disease include two inhibitors of catechol-O-methyltransferase (COMT), entacapone and tolcapone, which, by decreasing the elimination of levodopa, extend the duration of its effects. Increased 'on' time and less 'wearing-off' symptomatology can be expected with the use of these COMT inhibitors. Two non-ergot dopaminergic agonists (pramipexole and ropinirole) and a long-acting ergoline (cabergoline) are also being introduced. These dopaminergic agonists, like the ergot derivatives currently available (bromocriptine, lisuride, and pergolide), are useful as adjuncts to levodopa, and are also efficacious as monotherapies.

Topics: Antiparkinson Agents; Benzophenones; Benzothiazoles; Cabergoline; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Enzyme Inhibitors; Ergolines; Guidelines as Topic; Humans; Indoles; Nitriles; Nitrophenols; Parkinson Disease; Pramipexole; Thiazoles; Tolcapone; Treatment Outcome

Topics: Antiparkinson Agents; Benzophenones; Benzothiazoles; Humans; Indoles; Levodopa; Nitrophenols; Parkinson Disease; Pramipexole; Thiazoles; Tolcapone