Pramipexole--a new dopamine agonist for the treatment of Parkinson's disease.

Although L-DOPA is the current 'gold standard' for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing off, freezing, involuntary movements) for most patients with Parkinson's disease. Pramipexole is an aminothiazole dopamine agonist with selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Pramipexole's preferential affinity for the D3 receptor subtype could contribute to efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. Both in vitro and in vivo studies in animals suggest that pramipexole possesses numerous neuroprotective properties, including dopamine autoreceptor agonist properties, antioxidant properties, ability to block the mitochondrial permeability transition pore and the ability to stimulate the release of trophic factors. Clinical studies have demonstrated that pramipexole has excellent pharmacokinetic properties and that it is an effective monotherapy in treating early Parkinson's disease and an effective adjunctive therapy with L-DOPA in treating late Parkinson's disease. In addition, pramipexole has demonstrated efficacy in a clinical trial for the treatment of major depression. In the early disease studies, pramipexole was able to retard the need for L-DOPA treatment for several years. Thus, a new 'L-DOPA-sparing' paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and L-DOPA is added only as necessary.