title: Myths and realities of continuous dopaminergic stimulation.
abstract: Motor fluctuations and dyskinesia in later stages of Parkinson's disease (PD) are caused by pharmacokinetic as well as pharmacodynamic factors, intermittent dopaminergic stimulation being one of the most important. In the healthy brain, dopamine neurons in the substantia nigra pars compacta fire tonically at a steady rate of about 4 cycles/second. In later stages of PD, steady firing is replaced by pulsatile stimulation which causes molecular and physiologic changes in the basal ganglia. Continuous dopaminergic stimulation has been shown to dramatically improve motor fluctuations and dyskinesia by modifications of oral treatment (dopamine agonists, smaller, more frequent levodopa doses, controlled-release formulation of levodopa, addition of agents that slow down the catabolism of dopamine, such as inhibitors of catechol-O-methyl transferase and monoamine oxidase), transdermal delivery (rotigotine), infusion therapies (intravenous levodopa, subcutaneous application of apomorphine and lisuride, duodenal infusion of levodopa) and deep brain stimulation of the subthalamic nucleus.
authors: Department of Neurology, University Medical Centre, Zaloška 2, SI-1000 Ljubljana, Slovenia. zvezdan.pirtosek@kclj.si
authors: Zvezdan
authors: Z
authors: Pirtošek
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D003692:Delayed-Action Preparations; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007980:Levodopa / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008657:Metabolic Clearance Rate / Q000502:physiology; D009229:Mythology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D007980:Levodopa; D004298:Dopamine