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Repositioning Candidate Details

Candidate ID: R0069
Source ID: DB00268
Source Type: approved; investigational
Compound Type: small molecule
Compound Name: Ropinirole
Synonyms:
Molecular Formula: C16H24N2O
SMILES: CCCN(CCC)CCC1=C2CC(=O)NC2=CC=C1
Structure:
DrugBank Description: Ropinirole, also known as _ReQuip_, is a non-ergoline dopamine agonist used in Parkinson's disease and restless legs syndrome [FDA label], [A174547]. It is manufactured by GlaxoSmithKline Pharmaceuticals. Ropinirole was initially approved in 1997 by the FDA [FDA label] for the management of Parkinson's disease. In 2005, it was the first drug approved in the US for the management of primary moderate to severe restless legs syndrome [A174547]. In 2008, the extended-release capsules of ropinirole were approved, allowing for less frequent dosing, therefore increased compliance, and offering a similar side effect profile and efficacy to previous formulations of ropinirole [A35711].
CAS Number: 91374-21-9
Molecular Weight: 260.3746
DrugBank Indication: For the treatment of the signs and symptoms of Parkinson's disease and for the treatment of primary moderate-severe restless legs syndrome [FDA label].
DrugBank Pharmacology: **Effects on Parkinson's and restless leg syndrome** This drug promotes the relief or improvement of symptoms of Parkinson's or restless leg syndrome by stimulatory actions on dopamine receptors, which regulate movement. **Effects on blood pressure** Clinical experience with dopamine agonists, including ropinirole, suggests an association with impaired abilities in regulating blood pressure with resulting orthostatic hypotension, especially with patients undergoing dose escalation. In some patients in clinical studies, blood pressure changes were associated with orthostatic symptoms, bradycardia, and, in one case in a healthy volunteer, transient sinus arrest accompanied by syncope [FDA label]. The mechanism of orthostatic hypotension caused by ropinirole is assumed to be due to a D2-mediated blunting of noradrenergic response to a standing position, followed by a decrease in peripheral vascular resistance. Nausea is also a frequent symptom which accompanies orthostatic signs and symptoms [FDA label]. **Effects on prolactin** At oral doses as low as 0.2 mg, ropinirole suppressed serum prolactin concentrations in healthy male volunteers. Ropinirole had no dose-related effect on ECG wave form and rhythm in young, healthy, male volunteers in the range of 0.01 to 2.5 mg [FDA label]. **Effects on QT interval** Ropinirole had no dose- or exposure-related effect on average QT intervals in healthy male and female volunteers at doses up to 4 mg/day. The effect of ropinirole on QTc intervals at higher exposures reached either due to drug interactions, hepatic dysfunction, or at higher doses has not been adequately evaluated [FDA label].
DrugBank MoA: Ropinirole is a non-ergoline dopamine agonist. Ropinirole has the highest affinity at the D3 receptors, which are concentrated in the limbic areas of the brain and may be responsible for some of the neuropsychiatric effects [A35711]. The exact mechanism of action of ropinirole as a treatment for Parkinson’s disease is unknown, however, it is believed to be related to its ability to selectively stimulate dopamine D2 receptors within the caudate-putamen system in the brain. This system affects body movement. Negligible affinity is seen for ropinirole at α2 adrenoreceptors in the periphery and 5HT-1 receptor. Ropinirole has no affinity at the D1-like receptors, benzodiazepine or GABA receptors [A35711]. The precise mechanism of action of ropinirole as a treatment for Restless Legs Syndrome is unknown, however, it is believed to be related to its ability to stimulate dopamine receptors [FDA label].
Targets: Dopamine D3 receptor; Dopamine D2 receptor; Dopamine D4 receptor; Alpha adrenergic receptor
Inclusion Criteria: