Riluzole and experimental parkinsonism: antagonism of MPTP-induced decrease in central dopamine levels in mice.
We have investigated whether riluzole, a compound that interferes with glutamatergic (GLUergic) transmission, would protect central dopaminergic (DAergic) neurones from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the striatum in mice. MPTP decreased DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Riluzole protected against the MPTP-induced decrease in DA levels. The utilization of DA ([DOPAC+HVA]/DA) was increased after MPTP treatment, but returned to control values in mice given riluzole in combination with MPTP. Riluzole did not confer protection by inhibiting either monoamine oxidase type B activity or DA uptake. Possible mechanisms involved in the protective action of riluzole are discussed. Our results show that riluzole antagonizes the DAergic neurotoxicity of MPTP, a pro-parkinsonian neurotoxin, in mice.
Boireau
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A
Rhône-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, Département Biologie, Vitry-sur-Seine, France.
Dubédat
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P
Bordier
F
F
Peny
C
C
Miquet
J M
JM
Durand
G
G
Meunier
M
M
Doble
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D013844:Thiazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D019782:Riluzole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid