Riluzole and experimental parkinsonism

Boireau, A.; Dubédat, Pierre; Bordier, Frangoise; Pény, Colette; Miquet, Jean-Marie; Durand, G.; Meunier, Mireille; Doble, Adam

doi:10.1097/00001756-199412000-00063

Cited by 54 publications

(4 citation statements)

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“…Our finding, that riluzole protects dopamine neurones from cell death confirms and extends the data reported in rats with a unilateral 6-OHDA (6 μg) lesion which showed that a single riluzole injection (8 mg/kg) before lesion, and one twenty-four hours afterwards suppressed apomorphine or amphetamine-induced rotations and significantly reduced the loss of dopamine in the striatum [18]. Riluzole has also consistently been demonstrated to provide neuroprotection in MPTP-treated mice, when administered before the lesion [19-21]. In non-human primates riluzole administration either 1 hour prior to, or one hour after MPTP administration, followed by additional administrations also caused neuroprotection [22-25].…”

Section: Discussionsupporting

confidence: 76%

Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

2012

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BackgroundRiluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1. Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the median forebrain bundle.ResultsRats were treated with intraperitoneal riluzole (4 mg/kg or 8 mg/kg), 1 hour before the lesion then once daily for seven days. Riluzole produced a modest but significant attenuation of dopamine neurone degeneration, assessed by suppression of amphetamine-induced rotations, preservation of tyrosine hydroxylase positive neuronal cell bodies in the substantia nigra pars compacta and attenuation of striatal tyrosine hydroxylase protein loss. Seven days after 6-hydroxydopamine lesion, reactive astrocytosis was observed in the striatum, as determined by increases in expression of glial fibrillary acidic protein, however the glutamate transporter, GLT-1, which is also expressed in astrocytes was not regulated by the lesion.ConclusionsThe results confirm that riluzole is a neuroprotective agent in a rodent model of parkinson's disease. Riluzole administration did not regulate GLT-1 levels but significantly reduced GFAP levels, in the lesioned striatum. Riluzole suppression of reactive astrocytosis is an intriguing finding which might contribute to the neuroprotective effects of this drug.

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Section: Discussionsupporting

confidence: 76%

Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

2012

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“…In this sense, pedunculopontine tegmental nucleus (PPT) is one of the major source of glutamatergic afferences to nigrostriatal pathway 9 . Remarkably, the basal ganglia, including SNpc, and PPT share numerous similarities in projections to cortex, thalamus amygdala and brainstem 10 .…”

Section: Introductionmentioning

confidence: 99%

Absence of a synergic nigral proapoptotic effect triggered by REM sleep deprivation in the rotenone model of Parkinson´s disease

et al. 2019

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Excitotoxicity has been related to play a crucial role in Parkinson's disease (PD) pathogenesis. Pedunculopontine tegmental nucleus (PPT) represents one of the major sources of glutamatergic afferences to nigrostriatal pathway and putative reciprocal connectivity between these structures may exert a potential influence on rapid eye movement (REM) sleep control. Also, PPT could be overactive in PD, it seems that dopaminergic neurons are under abnormally high levels of glutamate and consequently might be more vulnerable to neurodegeneration. We decided to investigate the neuroprotective effect of riluzole administration, a N-methyl-D-aspartate (NMDA) receptor antagonist, in rats submitted simultaneously to nigrostrial rotenone and 24h of REM sleep deprivation (REMSD). Our findings showed that blocking NMDA glutamatergic receptors in the SNpc, after REMSD challenge, protected the dopaminergic neurons from rotenone lesion. Concerning rotenone-induced hypolocomotion, riluzole reversed this impairment in the control groups. Also, REMSD prevented the occurrence of rotenone-induced motor impairment as a result of dopaminergic supersensitivity. In addition, higher Fluoro Jade C (FJC) staining within the SNpc was associated with decreased cognitive performance observed in rotenone groups. Such effect was counteracted by riluzole suggesting the occurrence of an antiapoptotic effect. Moreover, riluzole did not rescue cognitive impairment impinged by rotenone, REMSD or their combination. These data indicated that reductions of excitotoxicity, by riluzole, partially protected dopamine neurons from neuronal death and appeared to be effective in relieve specific rotenone-induce motor disabilities.

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“…Oxcarbazepine (OCBZ, 2) is a relatively novel second-generation antiepileptic drug primarily used for the treatment of psychometric disturbance, 2 epilepsy, and trigeminal neuralgia, 3 and for Parkinson's disease. 4 In fact 2 was initially isolated as an active metabolite of 1, 5 and it is structurally a derivative of carbamazepine, adding an extra oxygen atom on the dibenzazepine ring. This small difference helps reduce the impact on the liver of metabolizing the drug.…”

Section: Introductionmentioning

confidence: 99%

A New Industrial Process for 10-Methoxyiminostilbene: Key Intermediate for the Synthesis of Oxcarbazepine

Singh

Gupta

Kumar

et al. 2009

Org. Process Res. Dev.

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A new industrial process, involving only two isolation and drying steps, for 10-methoxyiminostilbene (MISB), an advance intermediate of widely prescribed antiepileptic drug, oxcarbazepine, has been developed. A salient feature of this process is the novel use of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) to afford bromohydrin methyl ether from N-acetyliminostilbene. The byproducts of this process namely acetic acid, 5,5-dimethylhydantoin and Et 3 N • HBr are recyclable as well as nontoxic. This process is amenable for the large-scale production of MISB.

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Riluzole and experimental parkinsonism

Cited by 54 publications

References 0 publications

Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

Riluzole neuroprotection in a parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation

Absence of a synergic nigral proapoptotic effect triggered by REM sleep deprivation in the rotenone model of Parkinson´s disease

A New Industrial Process for 10-Methoxyiminostilbene: Key Intermediate for the Synthesis of Oxcarbazepine

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