Continuous dopamine-receptor stimulation in advanced Parkinson's disease.
Intermittent or pulsatile dopamine-receptor stimulation is postulated to induce plastic changes in motor systems that are responsible for the development of the motor fluctuations and dyskinesia that complicate long-term L-dopa therapy of Parkinson's disease. As a corollary to this hypothesis, continuous dopamine-receptor stimulation can avoid or reverse these complications. Such continuous stimulation is unlikely to mimic completely the normal function of the dopaminergic system, but should avoid the supra-physiological swings in extracellular dopamine that accompany intermittent L-dopa dosing. The concern is that this continuous stimulation might induce tolerance rather than sensitization to some effects of L-dopa. Open clinical trials support the value of continuous dopaminergic stimulation in Parkinson's disease with established motor complications, but rigorous studies, although experimentally difficult, are needed.
Nutt
J G
JG
Dept of Neurology, Oregon Health Sciences University, Portland 97201, USA.
Obeso
J A
JA
Stocchi
F
F
D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000009:adverse effects; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D020551:Pulse Therapy, Drug / Q000009:adverse effects*; D011954:Receptors, Dopamine / Q000187:drug effects; D012720:Severity of Illness Index
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D007980:Levodopa