Non-ergoline Dopamine Agonist Research Articles

Conversion from dopamine agonists to pramipexole

Pramipexole is a nonergoline dopamine agonist with D2 and preferential D3 dopamine receptor activity. This selective activity may result in clinically different effects. Small clinical trials indicate that overnight switching from one agonist to another can be performed safely. Objective To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinson's disease (PD). To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinson's disease (PD). Patients with advanced PD and motor complications not optimally controlled by levodopa and a stable dose of bromocriptine, pergolide or ropinirole were converted to pramipexole overnight. Clinical assessments were performed just prior to conversion and after 2, 6 and 12 weeks of treatment, when an optimal dose of pramipexole was achieved. Two hundred and seventeen patients were included in the trial. One hundred and twenty five were converted from pergolide to pramipexole, 58 from bromocriptine and 34 from ropinirole. After 12 weeks, the average dose of pramipexole was 2.8, 2.9 and 3.4 mg/d in patients converted from bromocriptine, pergolide, and ropinirole, respectively. UPDRS II, III and IV scores were reduced by 26-30% in all patients (p<0.0001). Mean levodopa dose was slightly reduced in all groups (p: NS). No serious or unexpected side effects were reported. The dose equivalences calculated from this trial were: bromocriptine:pramipexole 6.9:1, pergolide:pramipexole 0.9:1, ropinirole:pramipexole 1.5:1. Switching from bromocriptine, pergolide or ropinirole to pramipexole in an overnight schedule is safe. The observed clinical improvement may be related to a placebo effect, to the use of low doses of dopamine agonists or to a direct effect of pramipexole.

Ropinirole: for the treatment of restless legs syndrome.

Ropinirole is a non-ergoline dopamine agonist that exhibits a high affinity for D(2) and D(3) receptors but little or no affinity for D(1)-like and non-dopaminergic receptors. Symptoms of restless legs syndrome (RLS) [measured using the International Restless Legs scale and Clinical Global Impression-Global Improvement Scale scores] significantly improved with ropinirole compared with placebo in large, randomised, double-blind trials. Ropinirole reduced periodic leg movements and improved sleep efficiency relative to baseline and placebo in several trials (two of which were randomised, double-blind and relatively large) in patients with RLS. Ropinirole was generally well tolerated in patients with RLS; adverse events were generally mild to moderate in nature and consistent with those expected of dopamine agonists. Few patients receiving ropinirole withdrew from therapy because of adverse events, the most predominant of which were nausea and headache.

Management of Parkinson Disease

Parkinson disease is a movement disorder caused by progressive dopaminergic neuron degeneration in the substantia nigra and characterized by four cardinal symptoms: resting tremor, bradykinesia, rigidity, and postural instability. Levodopa has been considered the first-choice intervention for Parkinson disease for more than three decades. However, up to 50–90% of levodopa-treated patients develop motor complications within 5–10 years of starting treatment. It is important, therefore, to delay the initiation and/or reduce the dosage requirements of levodopa. The non-ergoline dopamine agonist ropinirole (Requip®) is used as monotherapy or in combination with low-dose levodopa in patients with early disease, and as an adjunct to levodopa in patients with advanced Parkinson disease.

Increased daytime sleepiness in Parkinson's disease: a questionnaire survey.

We evaluated the frequency and severity of excessive daytime sleepiness in an outpatient population with Parkinson's disease in comparison to age-matched controls and examined its relationship with antiparkinsonian drug therapy and sleep history. Increased daytime sleepiness and involuntary sleep episodes have been described in Parkinson's disease, but the etiology is not completely understood. The Epworth Sleepiness Scale (ESS), a validated questionnaire for daytime sleepiness, was prospectively administered to 99 consecutive outpatients with Parkinson's disease and 44 age-matched controls. In addition, a short sleep-screening questionnaire was used. The ESS revealed significantly increased daytime sleepiness in PD patients compared to controls (7.5 +/- 4.6 vs. 5.8 +/- 3.0, P = 0.013). The ESS score was abnormally high (10 or more) in 33 % of PD patients and 11.4% of controls (P = 0.001). ESS was not different between PD patients on levodopa monotherapy and those on levodopa and dopamine agonists, or between patients taking ergoline or non-ergoline dopamine agonists. In PD patients and in controls, sleepiness was significantly associated with reported heavy snoring. Increased daytime sleepiness is more frequent in patients with PD than in elderly controls. Similar to controls, increased daytime sleepiness in PD patients is correlated with heavy snoring.

Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study

Objective: To compare the tremorlytic properties of pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease. Methods: Eighty four patients with...

Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole

Periodic limb movement disorder (PLMD) occurs in a variety of sleep disorders and can cause insomnia as well as hypersomnia with daytime somnolence. The aim of this study was to investigate 12 untreated PLMD patients as compared with 12 normal controls and to measure the acute effects of 0.5 mg ropinirole (Requip((R))) - a non-ergoline dopamine agonist - as compared with placebo. In three nights (adaptation, placebo, ropinirole night) objective and subjective sleep and awakening quality were evaluated. In the target variable 'periodic leg movements per hour of sleep' (PLM/(hTST)) PLMD patients showed an increased value of 42/h (normal 0-5/h) with a greater number of arousals due to periodic leg movements (PLM) in sleep. They further demonstrated an increased number of awakenings, sleep stage S1, S4, stage shifts and decreased S2, but there were no significant differences concerning total sleep time, sleep efficiency (SE), subjective sleep quality and morning measures of mood, drive and drowsiness. However, measures of attention variability, numerical memory, fine motor activity and reaction time performance were impaired. Ropinirole 0.5 mg was shown to significantly improve the index PLM/(hTST) by 64% and arousals due to PLM, increase spontaneous arousals, REM-latency, stage 2 and stage shifts and decrease SREM. In the morning attention variability was attenuated and numerical memory augmented. Thus, ropinirole improved some sleep architecture and early morning measures of performance but specifically all PLM variables, which suggests a dopaminergic pathogenesis in PLMD. Copyright 2001 John Wiley & Sons, Ltd.

Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole

Periodic limb movement disorder (PLMD) occurs in a variety of sleep disorders and can cause insomnia as well as hypersomnia with daytime somnolence. The aim of this study was to investigate 12 untreated PLMD patients as compared with 12 normal controls and to measure the acute effects of 0.5 mg ropinirole (Requip®) – a non-ergoline dopamine agonist – as compared with placebo. In three nights (adaptation, placebo, ropinirole night) objective and subjective sleep and awakening quality were evaluated. In the target variable ‘periodic leg movements per hour of sleep’ (PLM/hTST) PLMD patients showed an increased value of 42/h (normal 0–5/h) with a greater number of arousals due to periodic leg movements (PLM) in sleep. They further demonstrated an increased number of awakenings, sleep stage S1, S4, stage shifts and decreased S2, but there were no significant differences concerning total sleep time, sleep efficiency (SE), subjective sleep quality and morning measures of mood, drive and drowsiness. However, measures of attention variability, numerical memory, fine motor activity and reaction time performance were impaired. Ropinirole 0.5 mg was shown to significantly improve the index PLM/hTST by 64% and arousals due to PLM, increase spontaneous arousals, REM-latency, stage 2 and stage shifts and decrease SREM. In the morning attention variability was attenuated and numerical memory augmented. Thus, ropinirole improved some sleep architecture and early morning measures of performance but specifically all PLM variables, which suggests a dopaminergic pathogenesis in PLMD. Copyright © 2001 John Wiley & Sons, Ltd.

Efficacy and tolerability of dopamine agonists in a parkinsonian population.

A clinical retrospective study was carried out in a population of 366 Parkinson's disease (PD) outpatients, to analyse the efficacy and tolerability of nonergoline and ergoline dopamine agonist (DA), in monotherapy or in combination with L-dopa. Safety was comparable in both groups except for higher occurrence of gastrointestinal symptoms in ergoline group and somnolence in nonergoline group. No significant difference concerning efficacy and tolerability was found during DA monotherapy. Mean age at PD onset was slightly higher in patients withdrawing DA monotherapy for adverse events comparing to patients who needed the addition of L-dopa (60.36 +/- 7.53 versus 54.88 +/- 10.75; p<0.05), suggesting that older age at the onset of the disease increases the risk for adverse events during DA monotherapy. The follow-up of the remaining patients still in monotherapy with DA will allow a better evaluation of these aspects.

Ropinirole: a review of its use in the management of Parkinson's disease.

Ropinirole, a non-ergoline dopamine agonist, has selective affinity for dopamine D2-like receptors and little or no affinity for non-dopaminergic brain receptors. Ropinirole is indicated as adjunct therapy to levodopa in patients with advanced Parkinson's disease. It is also indicated, and recent clinical trials have focused on its use, as monotherapy in patients with early Parkinson's disease. In the symptomatic treatment of early Parkinson's disease ropinirole monotherapy was significantly more effective than placebo in 2 multicentre, randomised, double-blind trials of 3 to 12 months duration as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and Clinical Global Impression/Clinical Global Evaluation Scales. In a similarly designed 3-year comparative study with bromocriptine, ropinirole recipients showed a significant improvement in UPDRS- activities of daily living (ADL) scores; however, motor scores were similar between the 2 groups. Ropinirole and levodopa treatments were similar in efficacy as measured by UPDRS ADL scores, although ropinirole recipients showed significantly less improvement on UPDRS motor scores at the 5-year study end-point in a multicentre, randomised double-blind trial. As an adjunct therapy to levodopa in patients with more advanced Parkinson's disease, ropinirole was reported to be as effective as bromocriptine and significantly more effective than placebo. In general in the comparisons with placebo ropinirole allowed a > or =20% reduction in the concomitant dose of levodopa without compromising efficacy in a significant proportion of patients and, in some trials decreased the amount of awake time spent in the 'off' state ('off' state is defined as a gradual return to parkinsonism despite adequate medication). Ropinirole was well tolerated either as monotherapy or as an adjunct to levodopa treatment. Nausea, dizziness and somnolence were the most commonly reported adverse events and were reported at a higher incidence by patients receiving ropinirole than by those receiving placebo. In patients with early Parkinson's disease, ropinirole generally showed a similar overall tolerability profile to bromocriptine although, over a 3-year period nausea was more commonly reported with ropinirole recipients. In a 5-year study, the incidence of dyskinesia was significantly lower with ropinirole than with levodopa regardless of levodopa supplementation. Prior to the addition of supplementary levodopa 5% of ropinirole recipients had experienced dyskinesia compared with 36% of those receiving levodopa. In patients with early Parkinson's disease, ropinirole monotherapy was more efficacious than bromocriptine with regard to improvement in activities of daily living, and need for supplemental levodopa. Ropinirole recipients had a higher requirement for levodopa supplementation than levodopa recipients in a 5-year study, but the incidence of dyskinesia was significantly lower with ropinirole than with levodopa (markedly so in the one third of ropinirole recipients who were able to remain on monotherapy with no levodopa supplementation). Thus available data suggest that ropinirole may provide a means of treating early Parkinson's disease while minimising the risk of dyskinesia and delaying the need for supplemental levodopa in some patients. In addition, ropinirole is also efficacious in the management of more advanced Parkinson's disease in patients who are experiencing motor complications after long term levodopa use.

Sleep Laboratory Studies in Restless Legs Syndrome Patients as Compared with Normals and Acute Effects of Ropinirole

Although the restless legs syndrome (RLS) is a disorder with a relatively high prevalence rate (8% in Austria) and leads to insomnia and excessive daytime tiredness, there is a paucity of sleep laboratory data concerning objective and subjective sleep and awakening quality. Thus, the aim of this study was to investigate 12 untreated RLS patients as compared with 12 normal controls and subsequently measure the acute effects of 0.5 mg ropinirole (Requip^®) – a nonergoline dopamine agonist – as compared with placebo. In 3 nights (adaptation, placebo, ropinirole night) sleep induction, maintenance and architecture were measured objectively by polysomnography, subjective sleep and awakening quality were assessed by self-rating scales and visual-analog scales, and objective awakening quality was evaluated by a psychometric test battery. In polysomnography, RLS patients demonstrated, as compared with normal controls, a decreased total sleep time (TST) and sleep efficacy, increased wakefulness during the total sleep period and frequency of nocturnal awakenings, increased sleep stage S1, decreased S2 and increased stage shifts. Subjective sleep quality tended to decrease, and morning well-being, mood, affectivity and wakefulness were deteriorated. In the noopsyche, fine motor activity and reaction time performance were deteriorated. Ropinirole 0.5 mg induced, as compared with placebo, an increase in TST, sleep efficacy, S2 sleep and stage shifts. In the morning, somatic complaints increased slightly, while fine motor activity and reaction time performance improved. Our findings suggest a key-lock principle in the diagnosis/treatment of RLS and a dopaminergic mechanism in its pathogenesis, which is supported by the data on periodic leg movements during sleep and arousals of the subsequent paper.

Pramipexole in the treatment of advanced Parkinson's disease.

Pramipexole is a novel nonergoline dopamine agonist with a preference for the dopamine D3 receptor subtype. Its efficacy and safety in the treatment of advanced Parkinson's disease has been investigated in several clinical studies. This review provides a summary of the data currently available, particularly in reference to the recent results of the European clinical phase III study and the potential tremorlytic activity of pramipexole. Interim analysis of the open-label European clinical phase III study has provided evidence of long-term efficacy and safety of pramipexole. In another study pramipexole has been shown to be significantly superior to placebo with an improvement in tremor score by 48% (vs. 13% in the placebo group). In addition to its likely usefulness in the treatment of rest tremor in Parkinson's disease, data suggest that pramipexole is of interest due to its reported low frequency of cardiovascular and gastrointestinal side-effects. However, studies comparing pramipexole with other antiparkinsonian agents would be useful to further define its benefits in the treatment of tremor-dominant Parkinson's disease and to further document its favourable adverse event profile.

Sleep Laboratory Studies in Restless Legs Syndrome Patients as Compared with Normals and Acute Effects of Ropinirole

The restless legs syndrome (RLS) is a common sensorimotor disorder which leads to severe sleep disturbances and showed a prevalence of 7.9% in our sleep laboratory. The aim of this study was to investigate periodic leg movements (PLM), arousal and respiratory variables in 12 untreated RLS patients and to measure the acute effects of 0.5 mg ropinirole, a nonergoline dopamine agonist, as compared with placebo. In the target variable PLM/h of total sleep time (PLM/h TST), RLS patients showed an increased value of 40/h (normal 0–5/h). Further, we found an increased number of PLM (368), PLM/h of time in bed (49/h), PLM/h of REM sleep (11), PLM/h of non-REM sleep (46) and PLM/h awake (61). The arousal index was also increased (32/h; normal 0–25/h), as were arousals due to PLM. In the confirmatory part of our descriptive data analysis, ropinirole 0.5 mg significantly improved, as compared with placebo, the index PLM/h TST by 75%. In the descriptive part, all the other PLM variables were improved as well. Arousals due to PLM decreased, while spontaneous arousals increased. Respiratory variables, which had a priori been in the normal range, showed a slight but significant improvement after the dopamine agonist. Thus, 0.5 mg ropinirole significantly improved the target variable PLM/h TST, along with objective and subjective sleep quality and morning noopsychic performance, as described in the preceding paper. Our data encourage further sleep studies including all above-mentioned variables in a larger group of RLS/PLM during sleep patients as well as long-term efficacy trials.

Comparative tolerability of the newer generation antiparkinsonian agents.

In recent years, the treatment of Parkinson's disease has undergone an immense amount of research, resulting in the development of multiple new medications. This has largely been fuelled by dissatisfaction over the development of motor complications secondary to long term levodopa therapy. Different treatment approaches are applied depending on the stage of Parkinson's disease. In early and mild Parkinson's disease, selegiline offers a limited symptomatic effect. Its neuroprotective effect, although at present theoretical, has questionable clinical relevance. Increased mortality associated with selegiline has been reported, although a meta-analysis of 5 different trials did not support this finding. The newer, non-ergoline dopamine agonists, pramipexole and ropinirole, have undergone extensive studies to evaluate their efficacy as monotherapy in early Parkinson's disease. These newer agonists are ideal initial symptomatic medications, primarily because they delay the onset of levodopa-induced motor fluctuations. Efficacy of the newer dopamine agonists in advanced disease seems to be comparable to that of the older agents, bromocriptine and pergolide. Adverse effects can be reduced by starting the medication at a very low dose and then slowly titrating upward. Catechol-O-methyl transferase (COMT) inhibitors are indicated for the treatment of motor fluctuations in advanced disease, particularly the 'wearing-off' phenomenon. Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in 'off' time. Unfortunately, 3 deaths have been observed, which are presumably secondary to tolcapone therapy. The drug has been withdrawn in many countries, and liver enzyme testing is mandatory in the US. Entacapone, a purely peripheral COMT inhibitor with a lower potency than tolcapone, has also proved to be effective and has not been associated with liver damage, obviating the need for testing.

Ropinirole and pramipexole, the new agonists.

Ropinirole and pramipexole are non-ergoline dopamine agonists which are relatively specific for the D2 family of dopamine receptors. They have side-effect profiles linked to peripheral and central dopaminergic stimulation, amenable to tolerance through a slow titration or the addition of domperidone in sensitive patients. They do not have the uncommon but problematic ergot-related side effects of bromocriptine and pergolide. Ropinirole and pramipexole have both been shown to be efficacious when used as monotherapy in early Parkinson's disease (PD), and have been suggested as being less likely than levodopa to lead to the early development of motor fluctuations and dyskinesias in this clinical setting. They have also been shown to be useful as adjunctive therapy to levodopa in advanced PD and to have a levodopa-sparing effect in these patients. Dose equivalents amongst the available dopamine agonists is difficult to know with certainty but has been estimated as follows: 30 mg of bromocriptine, 15 mg of ropinirole, 4.5 mg of pramipexole, and 3.0 mg of pergolide.

Ropinirole in the treatment of Parkinson’s disease

In this review, the pharmacokinetics, safety and tolerability, and clinical efficacy of ropinirole (Requip), a non-ergoline dopamine agonist approved for use in the treatment of Parkinson’s disease (PD) are examined. A summary of preclinical and clinical studies is presented. Ropinirole is safe and efficacious as monotherapy in the treatment of early PD [1-7] and as an adjunct to levodopa in more advanced cases [8-10].

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson’s disease: a double blind, placebo controlled, randomised, multicentre study

OBJECTIVESPramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance.METHODSSeventy eight patients of...

Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity

Pramipexole, a novel non-ergoline dopamine (DA) agonist, has been applied successfully for treatment of Parkinson's disease (PD). We report here that pramipexole can protect dopaminergic cell line Mes23.5 against dopamine- and levodopa-induced cytotoxicity possibly through a mechanism related to antioxidant activity. In the MES 23.5 cultures, DA and L-DOPA induce a dose- and time-dependent cytotoxicity, as determined by tetrazolium salt and trypan blue assays. Furthermore, an in situ terminal deoxynucleotidyl transferase assay demonstrates that DA-induced cell death is apoptotic. Pretreatment with pramipexole in a concentration range (4–100 μM) significantly attenuates DA- or L-DOPA-induced cytotoxicity and apoptosis, an action which is not blocked by D 3 antagonist U-99194 A or D 2 antagonist raclopride. Pramipexole also protects MES 23.5 cells from hydrogen peroxide-induced cytotoxicity in a dose-dependent manner. In cell-free system, pramipexole can effectively inhibit the formation of melanin, an end product resulting from DA or L-DOPA oxidation. These results indicate that pramipexole exerts its neuroprotective effect possibly through a mechanism, which is independent of DA receptors but related to antioxidation or scavenging of free radicals (e.g. hydrogen peroxide). As a direct DA agonist and potentially neuroprotective agent, pramipexole remains attractive in the treatment of PD.

Ropinirole: A dopamine agonist for the treatment of Parkinson’s disease

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, dosage and administration, and formulary considerations of ropinirole are reviewed. Ropinirole is a nonergoline dopamine agonist that binds to dopamine D2-receptors; the drug is indicated for use in the symptomatic treatment of early and late Parkinson's disease (PD). Ropinirole is rapidly absorbed after oral administration and undergoes extensive hepatic metabolism to active metabolites. The elimination half-life averages about six hours. Ropinirole has a low potential to interact with other drugs likely to be administered to PD patients. In patients with early PD, initial monotherapy with ropinirole was more effective than placebo or bromocriptine in the absence of selegiline and was as effective as bromocriptine in the presence of selegiline. Ropinirole was as effective as levodopa in patients with earlier stages of PD. In one subset of patients with advanced PD not adequately controlled by levodopa, adjunctive ropinirole was more effective than placebo and bromocriptine. Ropinirole was more effective than bromocriptine in patients previously given high-dose levodopa and was as effective in patients previously given low-dose levodopa or adjunctive dopamine agonist therapy. The most frequent adverse effects are nausea, somnolence, and dizziness; the dosage should be increased gradually to minimize adverse effects. Ropinirole is less expensive than bromocriptine and pergolide and similar in cost to pramipexole. Ropinirole appears to be a useful addition to existing therapeutic approaches to PD and is approved for both early and later stages of the disease.

Pramipexole. A review of its use in the management of early and advanced Parkinson's disease.

Pramipexole is an orally active non-ergoline dopamine agonist with selective activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes) and with preferential affinity for the D3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminished response to levodopa. The potential neuroprotective effects of pramipexole have been shown in animal and in vitro studies. Data from relatively long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to 6.0 mg/day) can improve activities of daily living and motor symptoms in patients with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodopa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test were not significantly improved. The extent of disability improved according to the UPDRS parts II and III but, when assessed by secondary efficacy parameters, it is unclear whether disability or the severity of disease improved. No significant differences were observed in patients randomised to pramipexole or bromocriptine according to a secondary hypothesis in a prospective study in which both drugs were better than placebo. Some quality-of-life measures improved with active treatment relative to placebo. Further studies comparing pramipexole with other dopamine agonists and levodopa in patients with early and advanced Parkinson's disease would be useful. In pramipexole recipients with early disease, the most commonly experienced adverse events were nausea, dizziness, somnolence, insomnia, constipation, asthenia and hallucinations. The most commonly reported adverse events in pramipexole recipients with advanced disease were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a worsening of the Parkinson's disease), dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency. The incidence of some adverse events did not greatly differ between pramipexole and placebo recipients. Pramipexole is effective as adjunctive therapy to levodopa in patients with advanced Parkinson's disease. However, the potential beneficial effects of pramipexole on disease progression need to be confirmed in clinical studies. The efficacy of pramipexole monotherapy in patients with early disease has also been demonstrated, although the use of dopamine agonists in early Parkinson's disease remains controversial.

Pharmacologic profile of ropinirole: a nonergoline dopamine agonist.

The use of dopamine agonists as monotherapy or in combination with levodopa in the treatment of Parkinson's disease (PD) allows for reduction or limitation of the levodopa dose, potentially delaying the onset or reducing the severity of late motor complications. Ropinirole is a new nonergoline dopamine agonist that binds specifically to D2-like receptors with a selectivity similar to that of dopamine (D3 > D2 > D4). The chemical structure of ropinirole has the potential to maintain a structure-activity relationship similar to that of dopamine and other effective dopamine agonists without producing ergot-related adverse effects. Ropinirole has demonstrated efficacy in two standard preclinical models of PD and has shown a very low propensity to induce dyskinesia in these studies. This latter property is of potential clinical importance for pharmacotherapy of early PD. This article will present the importance of pharmacologic specificity of dopamine agonists along with the basic pharmacologic characteristics of ropinirole that may contribute to its efficacy in the treatment of PD.