Ropinirole hydrochloride

Description

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.

Description

Ropinirole is a potent dopamine D₂ receptor agonist (K_i = 29 nM in a radioligand binding assay). It is selective for D₂ over D₁ dopamine receptors (K_i = >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.

Chemical properties

Off-White Solid

Originator

SmithKline Beecham (UK)

The Uses of Ropinirole hydrochloride

An antiparkinsonian agent. A selective dopamine D2-receptor agonist

The Uses of Ropinirole hydrochloride

antiparkinsonian;non-ergoline D2, D3, and D4 dopamine receptor agonist with highest affinity for D3

What are the applications of Application

Ropinirole Hydrochloride is a dopamine receptor agonist

Definition

ChEBI: Ropinirole hydrochloride is a member of indoles.

brand name

Requip (GlaxoSmithKline).

General Description

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.

Biological Activity

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.

Biochem/physiol Actions

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.

storage

Room temperature (desiccate)