Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson's disease.
Levodopa and the dopamine agonists are effective symptomatic treatments for Parkinson's disease, and all patients receive at least one of these agents during their illness. Long-term use of levodopa is commonly associated with motor complications such as dyskinesia, and both the dosing frequency and total daily dose of levodopa determine the rate of onset and severity. Dopamine agonists have gained popularity as first-line monotherapy in Parkinson's disease, as they effectively reverse motor deficits and reduce the risk of motor complications. Long-acting dopamine agonists providing continuous, rather than pulsatile, dopaminergic stimulation appear able to avoid dyskinesia induction. Current treatments act predominantly on D2 receptors, but drugs acting on both the D1 and D2 receptor families may produce an additive motor response, although this remains to be proven in patients with Parkinson's disease. Most currently used dopamine agonists are selective for D2-like receptors, with only pergolide and apomorphine potentially interacting with D1 receptor populations.
Jenner
Peter
P
Neurodegenerative Diseases Research Centre, Guy's, King's, and St Thomas' School of Biomedical Sciences, King's College, London, UK. div.pharm@kcl.ac.uk
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001667:Binding, Competitive / Q000187:drug effects; D018491:Dopamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007980:Levodopa