ReQuip was launched in the UK as a monotherapy or in combination with
low-dose levodopa for the treatment of early-stage idiopathic Parkinson's disease.
An eight step (24% overall yield) synthesis from isochroman provides access to
ropinirole. It is a non-ergot postsynaptic dopamine D2 agonist with activity in the
extrapyramidal system. It has weak or no significant activity at α2-adrenergic, 5-HT2
receptors and is inactive at 5-HT1, benzodiazepine, GABA, α1 and β adrenoreceptors.
Thus it has essentially no CNS side effects, fewer dyskinesias and on-off fluctuations.
In animals, it was able to reverse all motor deficits induced by MPTP. Tolerance is
not developed and ropinirole has similar postsynaptic potency to apomorphine but
with significantly less stereotyped behavior.
Ropinirole is a potent dopamine D2 receptor agonist (Ki = 29 nM in a radioligand binding assay). It is selective for D2 over D1 dopamine receptors (Ki = >100,000 nM) as well as a panel of adrenergic, serotonin, benzodiazepine, and GABA receptors (IC50s = >9,000 nM). Ropinirole reduces spontaneous locomotor activity in mice at doses less than 50 mg/kg but increases it at a dose of 100 mg/kg. It also induces contralateral asymmetry in an open field test in 6-OHDA-lesioned mice. Ropinirole (0.01-1 mg/kg) reverses locomotor deficits and restores interest in novel stimuli in a marmoset model of Parkinson''s disease induced by MPTP. Formulations containing ropinirole have been used for the treatment of Parkinson''s disease motor dysfunction.
antiparkinsonian;non-ergoline D2, D3, and D4 dopamine receptor agonist with highest affinity for D3
An antiparkinsonian agent. A selective dopamine D2-receptor agonist
ChEBI: Ropinirole hydrochloride is a member of indoles.
Requip (GlaxoSmithKline).
Ropinirole hydrochloride,4-(2-(dipropylamino)ethyl)indolin-2-one hydrochloride(Requip), is a white to pale greenish yellow powder that isvery soluble in water. Ropinirole is rapidly absorbed afteroral administration with maximal plasma concentrationsgenerally reached after about 1.5 hours, and the eliminationhalf-life appears to be approximately 3 hours. Ropinirole isalso rapidly and extensively distributed from the vascularcompartment and shows low plasma protein binding that isindependent of its plasma concentration. This drug iscleared by metabolism in the liver, with only 10% being excretedunchanged. The main metabolite of ropinirole is theN-despropyl metabolite. The glucuronide of this metaboliteand the carboxylic acid metabolite, 4-carboxymethylindolin-2-one, account only for 10% of the administered dose.None of the metabolites is pharmacologically active, and theexcretion of ropinirole-derived products is mainly via theurine. The main CYP450 isozyme involved in the metabolismof ropinirole is CYP1A2. Inhibitors or inducers ofthis enzyme have been shown to alter the clearance ofropinirole.Ropinirole is believed to act as an agonist atpostsynaptic D2 receptors. Ropinirole is indicated for thetreatment of the signs and symptoms of idiopathic PD andmoderate to severe primary RLS.
Selective D 2 -like receptor agonist (D 3 > D 2 > D 4 ). Causes biphasic spontaneous locomotor activity and contralateral circling in 6-OHDA-lesioned mice. Displays antiParkinsonian activity.
An agonist at the D2 and D3 dopamine receptor subtypes, binding with higher affinity to D3 than to D2 or D4. It has negligible effect on D1-receptors. It has medium in vitro affinity to opioid receptors. Ropinirole is said to have virtually no affinity to 5-HT1, 5-HT2, benzodiazepine, GABA, muscarinic, α1-, α2-, and β-adrenoreceptors. Used as antiparkinsonian drug.
Room temperature (desiccate)
