Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates

Exp Neurol. 2005 Mar;192(1):73-8. doi: 10.1016/j.expneurol.2004.11.013.

Abstract

Levodopa or short-acting dopamine (DA) agonist treatment of advanced parkinsonian patients exposes striatal DA receptors to non-physiologic intermittent stimulation that contributes to the development of dyskinesias and other motor complications. To determine whether continuous dopaminergic stimulation can delay or prevent onset of motor complications, four MPTP-lesioned, levodopa-naive cynomolgus monkeys were implanted subcutaneously with apomorphine containing ethylene vinyl acetate rods. Three other MPTP-lesioned monkeys received daily injections of apomorphine. Animals receiving apomorphine rods showed improved motor function ('ON' state) within 1 day of implantation, and remained continually 'ON' for the duration of treatment (up to 6 months) without developing dyskinesias. Injected animals also showed similar improvement in motor function after each apomorphine injection. However, these primates remained 'ON' for only 90 min and within 7-10 days all developed severe dyskinesias. Implanted monkeys evidenced local irritation, which was alleviated by steroid co-therapy.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / adverse effects
  • Apomorphine / administration & dosage*
  • Apomorphine / adverse effects
  • Apomorphine / blood
  • Disease Models, Animal
  • Dopamine Agonists / administration & dosage*
  • Dopamine Agonists / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Implants
  • Dyskinesias / etiology
  • Dyskinesias / prevention & control*
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Injections, Subcutaneous
  • Macaca fascicularis
  • Male
  • Movement / drug effects
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology
  • Polyvinyls / administration & dosage
  • Polyvinyls / adverse effects
  • Recovery of Function / drug effects
  • Steroids / therapeutic use

Substances

  • Antiparkinson Agents
  • Dopamine Agonists
  • Drug Implants
  • Polyvinyls
  • Steroids
  • ethylenevinylacetate copolymer
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Apomorphine