Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning "off"-L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries ("on" without dyskinesia, "on" with dyskinesia, and "off"). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications.
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PMID:Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease. 1139 Nov 28

Rotigotine is a new dopamine agonist with transdermal patch formulation for the treatment of Parkinson disease. The aim of this study was to investigate safety and efficacy of rotigotine in patients with early-stage Parkinson disease. In this open-label, dose-escalation, safety and efficacy study, 31 patients in the early stages of idiopathic Parkinson disease received rotigotine to a maximum of 18.0 mg/day. Of the 29 patients who completed the 28-day treatment phase, 24 were maintained at the maximum dose level. The drug was well tolerated, and skin reactions were mild. A statistically significant improvement in UPDRS I, II, and III scores was observed from baseline to end of treatment for the 29 subjects who completed the trial. Mean improvement (+/- standard deviation) was -0.41 +/- 0.78 on UPDRS I (P = 0.0078), -2.76 +/- 3.31 on UPDRS II (P = 0.0001), and -4.62 +/- 5.32 on UPDRS III (P < 0.0001). When results were stratified by maximum dose achieved, significant improvements were seen on all 3 subscores for patients achieving the maximum dose. These data suggest that rotigotine is a safe, well-tolerated, and effective treatment for early-stage Parkinson disease.
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PMID:Safety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease. 1596 7

Rotigotine is a non-ergot, enantio-selective, D3/D2/D1 dopamine (DA) agonist drug that is effective in classical models of Parkinson's disease (PD), including the reserpinised mouse, the 6-hydroxydopamine-lesioned rat, and the MPTP-treated primate. It is active after oral administration but shows high clearance and a relatively short duration of effect. However, rotigotine is also effective after transdermal application in 6-hydroxydopamine-lesioned rats and MPTP-treated monkeys, in both of which the duration of effect is markedly enhanced. The pharmacologic properties of rotigotine suggest that it has the characteristics necessary to form the basis of a transdermal treatment for the control of motor symptoms of PD.
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PMID:A novel dopamine agonist for the transdermal treatment of Parkinson's disease. 1603 Feb 91

Rotigotine is a nonergolinic dopamine D3/D2/D1 receptor agonist delivered via a transdermal system and has been evaluated for the treatment of idiopathic Parkinson's disease. Patients with early Parkinson's disease receiving rotigotine monotherapy experienced significantly greater improvements in parkinsonian symptoms (as measured by Unified Parkinson's Disease Rating Scale scores) compared to placebo in two large, well designed clinical trials. Significant beneficial effects versus placebo were observed with the 30 and 40 cm2 rotigotine patches in both trials.black triangle Patients with advanced Parkinson's disease receiving rotigotine as adjunctive therapy with levodopa experienced clinically significant reductions from baseline in 'off' time in two well designed clinical trials. In one trial, a large placebo effect was observed, therefore, there was no significant difference between placebo and active treatment (20, 40 and 60 cm2) for this primary efficacy variable, However, a recent study found a significant (p < or = 0.003) reduction in 'off' time in rotigotine 40 and 60 cm2 recipients versus that in the placebo group. Rotigotine was generally well tolerated in clinical trials as both monotherapy and when administered with levodopa; adverse events were generally mild or moderate in severity.
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PMID:Rotigotine: in Parkinson's disease. 1626 67

Rotigotine is a D3/D2/D1 dopamine agonist delivered through a silicone-based transdermal patch that is administered once daily. Pharmacokinetic data in humans have shown that steady-state plasma levels of rotigotine can be reached between 8 and 12 hours, and a stable drug release is maintained throughout the 24-hour patch application. Results of several clinical trials demonstrated that the rotigotine transdermal system is safe, well tolerated and effective monotherapy for patients in the early stages of Parkinson's disease. Rotigotine transdermal application also demonstrated the possibility of decreasing levodopa dosage in order to decrease its toxic effects in advanced Parkinson's disease. In addition, rotigotine has shown efficacy in the treatment of restless legs syndrome. Clinical studies on rotigotine, the first transdermally delivered dopamine agonist, are now in progress, and regulatory approval is expected in the near future.
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PMID:Rotigotine: a novel dopamine agonist for the transdermal treatment of Parkinson's disease. 1651 8

Rotigotine, an investigational dopamine agonist formulated as a patch, is being studied in Parkinson's disease. A microdialysis technique, in combination with microbore column liquid chromatography and electrochemical detection, was developed to monitor rotigotine levels in the brain. Microdialysis probes were inserted into the striata of anesthetized rats, and samples were collected during perfusion with Ringer's solution. Rotigotine was separated using a C18 reversed-phase column. The mobile phase consisted of 50mM Na(2)HPO(4) x 2H(2)O, 2.5 mM sodium octyl sulfonate, and pH 4.5; 35% volume to volume acetonitrile. The flow rate was 30 microl/min, and the potential of the glassy carbon electrode was set to +850 mV. The method allowed monitoring of the time course of brain extracellular rotigotine levels with a detection limit of 1 nM following either intravenous (0.5 mg/kg) or subcutaneous (5.0 mg/kg) rotigotine injection.
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PMID:Determination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection. 1697 91

Dopaminergic therapies, including levodopa and dopamine agonists, are the mainstays of therapy in Parkinson's disease. With the exception of the injectable short-acting dopamine agonist apomorphine, there is no other widely available non-oral dopaminergic therapy. Rotigotine is a lipid-soluble, non-ergot, D3, D2, D1 dopamine receptor agonist that has demonstrated efficacy as an alternative therapeutic option in both early and advanced Parkinson's disease. More importantly, it is uniquely formulated as a transdermal patch delivery system allowing for continuous, once-daily administration and better patient compliance. Preclinical and clinical trials have shown rotigotine to be a well-tolerated and effective treatment for early-stage Parkinson's disease. Rotigotine has also shown promise as adjunctive therapy with levodopa for the treatment of advanced Parkinson's disease.
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PMID:Rotigotine for the treatment of Parkinson's disease. 1700 15

Rotigotine is a nonergolinic dopamine D3/D2/D1-receptor agonist used clinically for the treatment of Parkinson's disease. This study aimed to determine the relationship between peak antiparkinsonian activity and drug plasma levels after administration of rotigotine to 1-methyl-4-phenyl-1,2,3,6-tetrahydropytidine-treated primates. Using single subcutaneous injections of rotigotine and blood sampling at two subsequent time points, the relationship between improvement in motor activity and plasma rotigotine level was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropytidine-treated common marmosets. Rotigotine (0.01875-0.3 mg/kg subcutaneously) produced an increase in locomotor activity even at the lowest dose tested. Total increase in motor activity and duration of drug effect were dose related. Motor disability was similarly improved by rotigotine in a dose-dependent manner. At the highest doses, hyperactivity and stereotypy were observed. Plasma concentrations of rotigotine were linearly related to dose over dosage range employed, but not to behavioral response. Results show that pulsatile administration of rotigotine effectively normalizes motor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropytidine-treated marmosets. Although dose and plasma concentrations of rotigotine are closely related, drug effects in the brain measured as locomotion and improvement of disability dissociate from plasma levels. Plasma levels corresponding to the optimal dose range (0.01875-0.075 mg/kg) will guide a continuous administration regimen of rotigotine in a subsequent study using the same experimental model of Parkinson's disease.
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PMID:Plasma levels of rotigotine and the reversal of motor deficits in MPTP-treated primates. 1735 22

Rotigotine, a non-ergolinic dopamine receptor agonist for treatment of Parkinson's disease was continuously administered over 48 h (0.5 mg/kg s.c., slow release formulation) to conscious rats striatally implanted with a microdialysis probe. Subsequently, the levels of rotigotine increased to a maximum of 3.42 + 2.1 nmol/l and remained at a level of 2.81 +/- 0.82 nmol/l for 48 h. Concomitantly, the dopamine levels consistently decreased to 20% of the control level. This suggests that the sustained administration of rotigotine provides stable extracellular drug levels in the striatum resulting in continuous stimulation of dopamine receptors.
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PMID:Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation. 1743 34

Dopamine agonists are effective in delaying levodopa-induced dyskinesia in early Parkinson's disease (PD) and reducing motor fluctuations in advanced PD. Rotigotine, a novel dopamine receptor agonist, improves motor function in both early and advanced PD using a transdermal route of administration. A smaller, but convincing body of data, supports its ability to ameliorate the symptoms of restless legs syndrome as well. The side-effect profile mimics other dopamine agonists, with the addition of application-site reactions, most of which are mild-to-moderate. Advantages over existing dopamine agonists include once-daily administration, absence of food interactions, maintenance of stable plasma levels and utility in patients with swallowing difficulties.
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PMID:Rotigotine transdermal patch in the treatment of Parkinson's disease and restless legs syndrome. 1756 66


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