Abstract
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.
Keywords
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Article info
Publication history
Accepted:
October 21,
1998
Received in revised form:
July 23,
1998
Received:
May 18,
1998
Identification
Copyright
© 1999 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
