PMID: 10727711: Protective effect of riluzole in the MPTP model of PD

[janet paterson <janet313@xxxxxxxxxxx>]

The protective effect of riluzole in the MPTP model of Parkinson's disease in 
mice
is not due to a decrease in MPP(+) accumulation.


Riluzole, has previously been shown to be protective in animal models of 
Parkinson's disease in vivo.

In the present study the effects of riluzole on the intrastriatal formation and 
accumulation of MPP(+), after i.p. injection of MPTP were tested in mice, using 
two different experimental protocols.

In the first protocol, mice were treated with a single dose (15 mg/kg i.p.) of 
MPTP and MPP(+) accumulation was measured 30 min, 1 h and 3 h after the 
injection of the toxin.

Riluzole (10 mg/kg p.o.), administered 30 min before MPTP, did not modify the 
accumulation kinetic of MPP(+).

Contrarily to riluzole, a single dose of 50 mg/kg p.o. of 7-nitroindazole 
(7-NI), a non-selective non hypertensive inhibitor of nitric oxide synthase 
(NOS), significantly decreased MPP(+) levels.

In the second protocol, consisting of 3 injections of MPTP (15 mg/kg i.p.), 
riluzole, administered 4 times at the dose of 5 mg/kg p.o., had no effect on 
MPP(+) levels.

The protective effect of repeated treatments of riluzole and 7-NI against 
MPTP-induced depletion of dopamine (DA) is also reported.

Our data obtained with 7-NI (in agreement with previous studies reported by 
others) suggest that a part of the protection observed with this NOS inhibitor 
is probably due to in vivo inhibition of monoamine oxidase-B (MAO-B).

That riluzole does not modify MPP(+) accumulation demonstrates that its 
protective effect against MPTP toxicity was not due to an in vivo interference 
with MPTP metabolism.


Neuropharmacology 2000 May  1;39(6):1016-1020
Boireau A, Dubedat P, Bordier F, Imperato A, Moussaoui S
Rhone-Poulenc Rorer S.A., Centre de Recherche de Vitry-Alfortville, 
Vitry-sur-Seine Cedex, France

PMID: 10727711

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janet paterson
53 now / 41 dx / 37 onset
a new voice: 
613 256 8340 PO Box 171 Almonte Ontario Canada K0A 1A0