indication

For the treatment of the signs and symptoms of idiopathic Parkinson's disease. Also used for the treatment of restless legs syndrome.

pharmacology

Ropinirole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D₂ subfamily of dopamine receptors, binding with higher affinity to D₃ than to D₂ or D₄ receptor subtypes. The relevance of D₃ receptor binding in Parkinson's disease is unknown. The mechanism of ropinirole-induced postural hypotension is presumed to be due to a D₂ -mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance.

mechanism of action

Ropinirole binds the dopamine receptors D₃ and D₂. Although the precise mechanism of action of ropinirole as a treatment for Parkinson's disease is unknown, it is believed to be related to its ability to stimulate these receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that ropinirole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum.

toxicity

Symptoms of overdose include agitation, chest pain, confusion, drowsiness, facial muscle movements, grogginess, increased jerkiness of movement, symptoms of low blood pressure (dizziness, light-headedness)upon standing, nausea, and vomiting.

biotransformation

Hepatic. Ropinirole is extensively metabolized to inactive metabolites via N -despropylation and hydroxylation pathways, largely by the P450 isoenzyme CYP1A2. N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%).

absorption

Absolute bioavailability is 55%, indicating a first pass effect. Food does not affect the extent of absorption.

half life

6 hours

route of elimination

Ropinirole is extensively metabolized by the liver to inactive metabolites, and less than 10% of the administered dose is excreted as unchanged drug in urine.

drug interactions

Ciprofloxacin: Ciprofloxacin may increase the effect and toxicity of ropinirole.

Fluvoxamine: Increases the effect and toxicity of ropinirole

Paliperidone: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, ropinirole. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Thiothixene: Thiothixene may antaonize the effects of the anti-Parkinsonian agent, Ropinirole. Consider alternate therapy or monitor for decreased effects of both agents.

Ziprasidone: The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, ropinirole. Consider alternate therapy or monitor for worsening of movement disorder.

Zuclopenthixol: Antagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and ropinirole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.