Abstract
Parkinson‘s disease (PD) is a complex neurodegenerative disease with both motor and nonmotor symptoms. The major clinical symptoms of PD are due to dopamine deficiency caused by the degeneration of nigrostriatal dopaminergic neurons. As a consequence, current treatments remain focused on the dopamine system. Dopamine-replacement therapy with levodopa has been the mainstay of symptomatic treatment of PD for nearly 40 years. However, levodopa-induced motor complications have led many physicians to advocate alternative options for treatment initiation in suitable patients or as an adjunctive therapy in more advanced cases.
Financial & competing interests disclosure
Heinz Reichmann served as an advisor to and received speaker fees from Boehriner Ingelheim. The author has received honoraria for Adv. Bd. or lectures from GSK, Pfizer, Eli Lilly, Novartis, TEVA, Lundbeck, Bayer Health Care, Solvay, Desitin, Cephalon and others.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Notes
Pramipexole has strong agonist activity on D2, D3 and D4 receptor subtypes. Dopamine receptors were originally characterized by ligand specificity and coupling to adenylate cyclase (D1 and D2); the D1 class stimulates the adenylate cyclase pathway while the D2 class inhibits it Citation[17]. Currently, five human dopamine receptors have been identified and are classified into two main receptor families: D1 (receptor subtypes D1 and D5) and D2 (receptor subtypes D2, D3 and D4). D1 and D2 receptors are mainly found in the striatum and the substantia nigra. D3 and D4 receptors are more selectively associated with the limbic brain areas, which receive their dopamine input from the ventral tegmental area and are known to be associated with cognitive, emotional and endocrine functions. D5 receptors are expressed in the hippocampus, the hypothalamus and the parafascicular nucleus of the thalamus and, thus, might be involved in affective, neuroendocrine or pain-related aspects of dopaminergic functions.
Ratio of binding affinity (Ki-values): the higher number, the higher the affinity for D3 versus D2.
Taken from Citation[77].
Taken from Citation[77].