Mechanism of Action: Ropinirole hydrochloride is a non-ergoline dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 and D3 dopamine receptor subtypes, binding with higher affinity to D3 than to D2 or D4 receptor subtypes.

Ropinirole has moderate in vitro affinity for opioid receptors. Ropinirole and its metabolites have negligible in vitro affinity for dopamine D1, 5-HT1, 5-HT2, benzodiazepine, GABA, muscarinic, alpha1-, alpha2-, and beta-adrenoreceptors.

Parkinson's Disease: The precise mechanism of action of ropinirole hydrochloride as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of postsynaptic dopamine D2-type receptors within the caudate-putamen in the brain. This conclusion is supported by studies that show that ropinirole improves motor function in various animal models of Parkinson's disease. In particular, ropinirole attenuates the motor deficits induced by lesioning the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in primates. The relevance of D3 receptor binding in Parkinson's disease is unknown.

Restless Legs Syndrome (RLS): The precise mechanism of action of ropinirole hydrochloride as a treatment for Restless Legs Syndrome (also known as Ekbom Syndrome) is unknown. Although the pathophysiology of RLS is largely unknown, neuropharmacological evidence suggests primary dopaminergic system involvement. Positron emission tomographic (PET) studies suggest that a mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.

Clinical Pharmacology Studies: In healthy normotensive subjects, single oral doses of ropinirole hydrochloride in the range 0.01 to 2.5 mg had little or no effect on supine blood pressure and pulse rates. Upon standing, ropinirole hydrochloride caused decreases in systolic and diastolic blood pressure at doses above 0.25 mg. In some subjects, these changes were associated with the emergence of orthostatic symptoms, bradycardia, and, in one case, transient sinus arrest with syncope. With repeat dosing and slow titration up to 4 mg once daily in healthy volunteers, postural hypotension or hypotension-related adverse events were noted in 13% of subjects on ropinirole hydrochloride and none of the subjects on placebo.

The mechanism of postural hypotension induced by ropinirole hydrochloride is presumed to be due to a D2-mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance. Nausea is a common concomitant symptom of orthostatic signs and symptoms.

At oral doses as low as 0.2 mg, ropinirole hydrochloride suppressed serum prolactin concentrations in healthy male volunteers.

Ropinirole hydrochloride 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.

Ropinirole hydrochloride had no dose- or exposure-related effect on mean QT intervals in healthy male and female volunteers titrated to doses up to 4 mg/day. The effect of ropinirole hydrochloride on QT intervals at higher exposures achieved either due to drug interactions or at doses used in Parkinson's disease has not been systematically evaluated.