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

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

Publication date: Mar 20, 2020

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.

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.

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.

Over 60?days of a continuous circadian i.c.v. of A-dopamine improved motor symptoms (therapeutic index from 30 to 90?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.

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

Open Access PDF

Moreau, C., Rolland, A.S., Pioli, E., Li, Q., Odou, P., Barthelemy, C., Lannoy, D., Demailly, A., Carta, N., , Deramecourt, Auger, F., Kuchcinski, G., Laloux, C., Defebvre, L., Bordet, R., Duce, J., Devedjian, J.C., Bezard, E., Fisichella, M., and David, D. Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson’s disease. 24456. 2020 Neurobiol Dis.

Concepts Keywords
Anaerobic Levodopa-induced dyskinesia
Anaerobically MPTP
Catheter L-DOPA
Circadian TAAR1 agonists
Dopa RTT
Dopamine Prodrugs
Dyskinesia Catecholamines
Effective Dose Dopamine agonists
Ester Branches of biology
Infusion Drugs
Intracerebroventricular Catheter
Methyl
MPTP
Oxidation
Parkinson
Phenyl
Primate
Primates
Subcutaneous
Symptomatic Treatment

Semantics

Type Source Name
drug DRUGBANK Dopamine
drug DRUGBANK Levodopa
disease MESH dyskinesia
disease MESH Death

Original Article

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