Disease relevance of C07564

• CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary [1].
• CONCLUSIONS: Use of ropinirole seems to be associated with a higher risk of hypotension and somnolence than use of pramipexole when compared with placebo [2].
• In a model of kainate-induced epilepsy, ropinirole or DHECP did not affect seizure parameters, but reduced mortality rate [3].
• Dopamine agonists suppress cholinomimetic-induced tremulous jaw movements in an animal model of Parkinsonism: tremorolytic effects of pergolide, ropinirole and CY 208-243 [4].
• These behavioral and neurochemical findings suggest that ropinirole and DHECP may exert either protective activity (as found in animals pretreated with these drugs and exposed to hypobaric hypoxia) or reversal of brain injury (as found in animals treated after two-month occlusive brain ischemia) [3].

Psychiatry related information on C07564

• Ropinirole therapy was not associated with daytime episodes of rapid eyes movement (REM) sleep [5].
• STUDY OBJECTIVES: Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS) [6].
• The behavioral tests showed that the locomotor activities were increased significantly in the mice treated with iron-deficiency (ID) diet and 6-OHDA lesions, which were reversed by the D2/D3 agonist ropinirole [7].
• Use of pramipexole seems to be associated with a higher risk of hallucinations than use of ropinirole when compared with placebo [2].
• 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 [8].

High impact information on C07564

• METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease [1].
• Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study [9].
• A blinded, central, region-of-interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with ropinirole (-13.4%; n = 68) compared with levodopa (-20.3%; n = 59; 95% confidence interval [CI], 0.65-13.06) [9].
• Statistical parametric mapping localized lesser reductions in (18)F-dopa uptake in the putamen and substantia nigra with ropinirole [9].
• The dopamine agonists (DA) pramipexole and ropinirole were recently implicated in causing "sleep attacks" and motor vehicle accidents [10].

Chemical compound and disease context of C07564

• Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using (18)F-dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa [9].
• Pramipexole, ropinirole, and mania in Parkinson's disease [11].
• Chronic administration of L-DOPA to MPTP-treated common marmosets induces marked dyskinesia while repeated administration of equivalent antiparkisonian doses of ropinirole and bromocriptine produces only mild involuntary movements [12].
• We focused our studies on four dopaminergic ligands that are used in the treatment of Parkinson's disease: bromocriptine, pergolide, piribedil, and ropinirole [13].
• The dopamine D2 receptor antagonist, domperidone, caused hypertension in ropinirole-but not vehicle-treated rats [14].

Biological context of C07564

• Clinical pharmacokinetics of ropinirole [15].
• Ropinirole shows low plasma protein binding [15].
• Controversial reports of sudden onset 'sleep attacks' resulting in road traffic accidents have recently been reported in patients with Parkinson's disease (PD) taking the non-ergot dopamine D(2 )/D(3) receptor agonists pramipexole and ropinirole [16].
• 2. Single doses of 800 micrograms ropinirole did not cause clinically significant changes in supine resting heart rate and blood pressure [17].
• The pathways of metabolism after incubation of ropinirole with human liver microsomes were N-despropylation and hydroxylation [18].

Anatomical context of C07564

• Similar effects can be observed after incubating with the conditioned medium derived from PPX- and ROP-treated substantia nigra astroglia [19].
• We evaluated the effects of four DAs (pergolide, cabergoline, ropinirole, pramipexole) on morphology and function of heart valves in patients with Parkinson's disease (PD) to determine the frequency and clinical relevance of DA-induced VHD [20].
• Additionally, incubation of ropinirole with microsomes derived from CYP1A2 transfected cells readily produced the N-despropyl and hydroxy metabolites [18].
• The long-duration effect of L-DOPA and ropinirole may, therefore, be due to some slowly evolving postsynaptic pharmacodynamic change in the central nervous system (CNS) [21].

Associations of C07564 with other chemical compounds

• Limited evidence suggests that some dopaminergic agents, such as levodopa/carbidopa, pergolide, and ropinirole, may be effective in children with RLS associated with ADHD symptoms [22].
• The CYP1A2 inhibitor ciprofloxacin produced increases in the plasma concentrations of ropinirole when these 2 drugs were coadministered, but no interaction was seen with theophylline which, like ropinirole, is also a substrate for CYP1A2 [15].
• In rats with a unilateral, 6-hydroxydopamine lesion of the substantia nigra, S32504 (0.0025-0.04 mg/kg, s.c.) more potently elicited contralateral rotation than S32601 [(-)-trans-3,4,4a,5,6, 10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth-[1,2-b]-1,4-oxazine (its less active enantiomer)], ropinirole, and l-3,4-dihydroxyphenylalanine (l-DOPA) [23].
• Talipexole and the ropinirole metabolite, SKF-104557, were partial agonists at the hD4 receptor [24].
• Ropinirole is a modern dopamine agonist with a halflife of medium extent that is highly selective for D(2)-receptors [25].

Gene context of C07564

• However, partial inhibition was observed between ropinirole and CYP1A2 and pergolide and CYP3A4 [26].
• In contrast, potent interactions were observed between CYP2D6 and pergolide and ropinirole, as well as with CYP3A4 and bromocriptine [26].
• Thus, it could be concluded that the major P450 enzyme responsible for ropinirole metabolism at lower (clinically relevant) concentrations is CYP1A2 with a contribution from CYP3A, particularly at higher concentrations [18].
• Of the dopamine receptor agonists tested, three drugs, ropinirole, pergolide, and bromocriptine, were found to inhibit the activity of at least one human cytochrome P450 enzyme, while the remaining dopamine agonist, pramipexole, was devoid of any potent P450 interaction [26].
• Ropinirole is a selective non-ergoline dopamine D2 receptor agonist indicated for use in treating Parkinson's disease [15].

Analytical, diagnostic and therapeutic context of C07564

• The authors document, in a placebo-controlled, randomized, double-blind, crossover study performed in 20 healthy volunteers, using the Multiple System Latency Test (MSLT) as primary outcome, that ropinirole reduces time to sleep onset in humans [5].
• The starting dose of ropinirole was 0.25 mg tid with titration to at least 1.5 mg tid (maximum dose, 8 mg tid) [27].
• SETTING: Ambulatory care at 22 different sites in the United States. PATIENTS: Patients who successfully completed the initial 6-month study could enter the 6-month extension study (ropinirole, n = 70; placebo, n = 77) [28].
• Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease: a meta-analysis [2].
• Clinical trials to assess putative neuroprotective effects are also on going with ropinirole and pramipexole [29].

References