Parkinson's Disease Session: PDF OnlyPramipexole: A Dopamine-Receptor Agonist for Treatment of Parkinson's DiseaseMierau, Joachim Author Information Department of Biochemical Research, Boehringer Ingelheim KG, Ingelheim, Germany Pramipexole is a discovery of Boehringer Ingelheim KG research, which is being co-developed with The Upjohn Company. Address correspondence and reprint requests to Dr. J. Mierau at Boehringer Ingelheim KG, Department of Biochemical Research, Binger Strasse, D-55216 Ingelheim, Germany. Clinical Neuropharmacology: Volume 18 - Issue - p S195-S206 Buy Abstract Pramipexole is a potent agonist at both presynaptic autoreceptors and noninnervated dopamine (DA) CNS receptors. These characteristics are demonstrated by potent inhibition of DA synthesis and release and by reduction in the dopaminergic firing rate. Pramipexole has also proven highly effective in animal models in which the dopaminergic afferents to the striatum have been destroyed. In rats with unilateral lesions of the medial forebrain bundle, pramipexole has a potent stimulatory effect. In monkeys pretreated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, parkinsonian symptoms are fully antagonized by intramuscular pramipexole in doses below 0.1 mg/kg, thus predicting a high antiparkinsonian potential. In addition, an antidyskinetic action of pramipexole was shown in haloperidol-sensitized rhesus monkeys; the dose that fully relieved the symptoms in 50% of the animals was 0.1 mg/kg. Receptor-binding experiments and functional assays have characterized pramipexole as a full DA-receptor agonist with specificity for the D2-receptor subfamily. This affinity profile is uniformly selective for the S(-) enantiomer, which is pramipexole. Within the D2-receptor subfamily, pramipexole binds with highest affinity to D3 receptors (Ki = 0.5 nmol/L), indicating a seven- and tenfold greater selectivity for D3 receptors compared with D2 and D4 receptors. By contrast, other DA-receptor agonists, such as quinpirole and bromocriptine, are nonselective or are more selective for D2/D4 receptors. The receptor affinity ratio of pramipexole (D3 > D2L = D2s > D4) has been confirmed by saturation binding experiments and by its potency in functional activation of the receptor subtypes. © Williams & Wilkins 1995. All Rights Reserved.