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Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates.

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.
AuthorsFrancesco Bibbiani, Lauren C Costantini, Raj Patel, Thomas N Chase
JournalExperimental neurology (Exp Neurol) Vol. 192 Issue 1 Pg. 73-8 (Mar 2005) ISSN: 0014-4886 [Print] United States
PMID15698620 (Publication Type: Journal Article)
Chemical References
  • Antiparkinson Agents
  • Dopamine Agonists
  • Drug Implants
  • Polyvinyls
  • Steroids
  • ethylenevinylacetate copolymer
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Apomorphine
Topics
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Antiparkinson Agents (administration & dosage, adverse effects)
  • Apomorphine (administration & dosage, adverse effects, blood)
  • Disease Models, Animal
  • Dopamine Agonists (administration & dosage, adverse effects)
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Implants
  • Dyskinesias (etiology, prevention & control)
  • Inflammation (chemically induced, drug therapy)
  • Injections, Subcutaneous
  • Macaca fascicularis
  • Male
  • Movement (drug effects)
  • Parkinsonian Disorders (complications, drug therapy, physiopathology)
  • Polyvinyls (administration & dosage, adverse effects)
  • Recovery of Function (drug effects)
  • Steroids (therapeutic use)

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