Pramipexole is an amino-benzothiazole–type dopamine agonist. It binds to presynaptic and postsynaptic dopamine D2 and D3 receptors, but does not have affinity for the dopamine D1 receptor site.
Pharmacodynamics. Pramipexole stimulates presynaptic and postsynaptic dopamine D2 receptors in a dose-dependent manner and reduces extracellular concentrations of dopamine by inhibiting dopamine synthesis and release. Although not proven, the motor benefits of pramipexole in Parkinson disease are likely due to dopamine D2 stimulation, whereas its effects on mood and apathy may be related to its D3 agonist properties. Pramipexole has a relatively high affinity for a2 adrenoreceptors but has little effect on other neurotransmitter systems. In addition to an antiparkinsonian effect, it is considered to have a neuroprotective effect demonstrated by prevention of levodopa-induced toxicity in vitro. The possible mechanisms are as follows:
A review of various studies shows that neuroprotection requires treatment prior to neurologic insult and high concentrations of pramipexole are required (Albrecht and Buerger 2009).
Pharmacokinetics. Pramipexole exhibits linear pharmacokinetics over the dose range of 0.125 to 1.5 mg administered every 8 hours in healthy volunteers. Plasma concentrations of pramipexole are proportional to dose. The plasma elimination half-life is approximately 7 to 9 hours, sufficiently long to make it a practical drug for oral administration in Parkinson disease patients with short-duration levodopa responses. Pramipexole is excreted by the renal organic transport system and renal clearance accounts for about 80% of the total clearance of an oral dose.
Formulations. An extended-release formulation of pramipexole is available for use as a once-daily oral treatment for Parkinson disease, and the effects are equal to that of 3-times-daily immediate release pramipexole (Chwieduk and Curran 2010).
Pharmacogenetics. DRD3 Ser9Gly gene polymorphisms are significantly associated with the therapeutic efficacy of pramipexole in Chinese patients with Parkinson disease (Liu et al 2009).