Continuous dopamine-receptor treatment of Parkinson's disease: scientific rationale and clinical implications

Lancet Neurol. 2006 Aug;5(8):677-87. doi: 10.1016/S1474-4422(06)70521-X.

Abstract

Levodopa-induced motor complications are a common source of disability for patients with Parkinson's disease. Evidence suggests that motor complications are associated with non-physiological, pulsatile stimulation of dopamine receptors. In healthy brains, dopamine neurons fire continuously, striatal dopamine concentrations are relatively constant, and there is continuous activation of dopamine receptors. In the dopamine-depleted state, standard levodopa therapy does not normalise the basal ganglia. Rather, levodopa or other short-acting dopaminergic drugs induce molecular changes and altered neuronal firing patterns in basal ganglia neurons leading to motor complications. The concept of continuous dopaminergic stimulation proposes that continuous delivery of a dopaminergic drug will prevent pulsatile stimulation and avoid motor complications. In monkeys treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and patients with Parkinson's disease, long-acting or continuous infusion of a dopaminergic drug reduces the risk of motor complications. The current challenge is to develop a long-acting oral formulation of levodopa that provides clinical benefits but avoids motor complications.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Basal Ganglia / drug effects
  • Basal Ganglia / pathology
  • Basal Ganglia / physiopathology
  • Disease Models, Animal
  • Dopamine Agents / pharmacology
  • Dopamine Agents / therapeutic use
  • Drug Administration Schedule
  • Dyskinesia, Drug-Induced / etiology
  • Humans
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Neural Networks, Computer
  • Parkinson Disease / drug therapy*
  • Receptors, Dopamine / physiology*

Substances

  • Antiparkinson Agents
  • Dopamine Agents
  • Receptors, Dopamine
  • Levodopa