PRAMIPEXOLE - A REVIEW OF ITS USE IN THE MANAGEMENT OF EARLY AND ADVANCED PARKINSONS-DISEASE

Pramipexole is an orally active non-ergoline dopamine agonist with sel ective activity at dopamine receptors belonging to the D2 receptor sub family (D-2, D-3, D-4 receptor subtypes) and with preferential affinit y for the D-3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminishe d response to levodopa. The potential,neuroprotective effects of prami pexole have been shown in animal and in vitro studies. Data from relat ively long term (10- or 31-week) studies suggest that pramipexole mono therapy (0.375 to 6.0 mg/day) cart improve activities of daily living and motor symptoms in patients,with early Parkinson's disease. Pramipe xole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodo pa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allow ed a reduction in levodopa dosage. Mentation, behaviour and mood [Unif ied Parkinson's Disease Rating Scale (UPDRS) part I], and timed walkin g test were not significantly improved. The extent of disability impro ved according to the UPDRS parts II and III but, when assessed by seco ndary efficacy parameters,, it is unclear whether disability or the se verity of disease improved. No significant differences were observed i n patients randomised to pramipexole or bromocriptine according to a s econdary hypothesis in a prospective study in which both drugs were be tter than placebo. Some quality-of-life,measures improved with active treatment relative to placebo. Further studies comparing pramipexole w ith other dopamine agonists and levodopa in patients with early and ad vanced Parkinson's disease would be useful.In pramipexole recipients w ith early disease, the most commonly experienced adverse events were n ausea, dizziness, somnolence, insomnia, constipation, asthenia and hal lucinations. The most commonly reported adverse events in pramipexole recipients with advanced disease were orthostatic hypotension, dyskine sias, extrapyramidal syndrome (defined as a worsening of the Parkinson 's disease), dizziness, hallucinations, accidental injury; dream abnor malities, confusion, constipation, asthenia, somnolence, dystonia, gai t abnormalities hypertonia, dry mouth, amnesia and urinary frequency. The incidence of some adverse events did not greatly differ between pr amipexole and placebo recipients. Conclusions. Pramipexole is effectiv e as adjunctive therapy to levodopa in patients with advanced Parkinso n's disease. However; the potential beneficial effects of pramipexole on disease progression need to be confirmed in clinical studies. The e fficacy of pramipexole monotherapy in patients with early disease has also been demonstrated, although the use of dopamine agonists in early Parkinson's disease remains controversial.