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Pramipexole protects against MPTP toxicity in non‐human primates
Author(s) -
Iravani Mahmoud M.,
Haddon Claire O.,
Cooper J. Mark,
Jenner Peter,
Schapira Anthony H.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03625.x
Subject(s) - pramipexole , mptp , substantia nigra , dopaminergic , pars compacta , pharmacology , dopamine , dopamine receptor d3 , parkinson's disease , neurotoxin , tyrosine hydroxylase , agonist , biology , endocrinology , medicine , receptor , disease
The neurotoxin MPTP induces nigral dopaminergic cell death in primates and produces a partial model of Parkinson's disease (PD). Pramipexole is a D 2 /D 3 dopamine receptor agonist used in the symptomatic treatment of PD, and which also protects neuronal cells against dopaminergic toxins in vitro . We now demonstrate that pramipexole partially prevents MPTP toxicity in vivo in a primate species. Common marmosets were repeatedly treated with pramipexole either before, coincidentally with, or after low‐dose MPTP treatment designed to induce a partial lesion of the substantia nigra. Animals pretreated with pramipexole had a significantly greater number of surviving tyrosine hydroxylase (TH) positive neurones in the pars compacta of the substantia nigra. Pramipexole pretreatment also prevented degeneration of striatal dopamine terminals. Treatment with pramipexole concurrently with MPTP or following MPTP did not prevent TH‐positive cell loss. Pramipexole pretreatment appears to induce adaptive changes that protect against dopaminergic cell loss in primates.