Riluzole as a Neuroprotective Therapy in Animal Models of Parkinson’s Disease
Riluzole is an anti-excitotoxic substance with sodium channel blocking properties that has been shown to possess neuroprotective activities in a wide variety of animal models of neurodegeneration including models of amyotrophic lateral sclerosis (ALS), Huntington’s disease, ischaemia and trauma. Riluzole is currently approved for the treatment of patients suffering from ALS. Studies in rodents have shown that riluzole is able to counteract toxin-induced degeneration of nigro-striatal neurons. For example, dosage of mice brain for dopamine (DA) content by HPLC indicate that riluzole prevents the diminution of striatal DA levels induced by co-treatment with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP). Similarly, riluzole attenuates the turning behavior produced by administration of apomorphine or amphetamine to rats that have received an unilateral injection of 6-hydroxydopamine. Behavioral and histological experiments were conducted in marmosets to investigate the antiparkinsonian profile of riluzole in primates. Systemic administration of a low doses regimen of MPTP (2 mg/kg subcutaneously twice, 1 week apart) produced a slowly evolving parkinsonian syndrome as evidenced by quantification of locomotor activity via computerized image analysis and clinical examination using a neurological evaluation scale. Administration of riluzole (10 mg/kg orally twice daily) significantly attenuated the locomotor alterations produced by the toxin. This effect was protracted over the 18 day observation period, at the end of which the brain of the animals was fixed for histobogical examination. Analysis of tyrosine hydroxylase immunofluorescence and cresylviolet staining revealed a significant preservation of the density of dopaminergic cells in the substantia nigra pars compacta (SNpc).