Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson's disease

Neurobiol Dis. 2020 Jun:139:104846. doi: 10.1016/j.nbd.2020.104846. Epub 2020 Mar 20.


Background: Continuous compensation of dopamine represents an ideal symptomatic treatment for Parkinson's disease (PD). The feasibility in intracerebroventricular administration (i.c.v.) of dopamine previously failed because of unresolved dopamine oxidation.

Objectives: We aim to test the feasibility, safety margins and efficacy of continuous i.c.v. of anaerobic-dopamine (A-dopamine) with a pilot translational study in a non-human primate model of PD.

Methods: Continuous and circadian i.c.v. of A-dopamine was administered through a micro-pump connected to a subcutaneous catheter implanted into the right frontal horn of 8 non-human primates treated with 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP). A-dopamine was assessed at acute doses previously reported for dopamine as well as evaluating the long term therapeutic index of A-dopamine in comparison to anaerobically prepared L-dopa or methyl ester L-dopa.

Results: Over 60 days of a continuous circadian i.c.v. of A-dopamine improved motor symptoms (therapeutic index from 30 to 70 mg/day) without tachyphylaxia. No dyskinesia was observed even with very high doses. Death after 1 to 10 days (without neuronal alteration) was only observed with doses in excess of 160 mg whereas L-dopa i.c.v. was not effective at any dose. The technical feasibility of the administration regimen was confirmed for an anaerobic preparation of dopamine and for administration of a minimal infusion volume by micro-pump at a constant flow that prevented obstruction.

Conclusion: Continuous circadian i.c.v. of A-dopamine appears to be feasible and shows efficacy without dyskinesia with a safe therapeutic index.

Keywords: Continuous dopaminergic stimulation; Dopamine in anaerobia; Motor fluctuations with dyskinesia; Neurosurgical treatment; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Antiparkinson Agents / pharmacology
  • Disease Models, Animal
  • Dopamine / administration & dosage*
  • Dopamine Agonists / pharmacology
  • Dyskinesia, Drug-Induced / drug therapy
  • Infusions, Intraventricular*
  • Levodopa / analogs & derivatives
  • Levodopa / pharmacology
  • Macaca
  • Male
  • Motor Activity / drug effects*
  • Parkinson Disease / drug therapy*
  • Parkinsonian Disorders / drug therapy
  • Pilot Projects


  • Antiparkinson Agents
  • Dopamine Agonists
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • levodopa methyl ester
  • Dopamine