Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)

Miller, Robert G.; Mitchell, J D; Lyon, Mary; Moore, Dan H.

doi:10.1002/14651858.cd001447.pub2

Cited by 375 publications

(328 citation statements)

References 28 publications

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“…Eleven patients presented the bulbar form of the disease, and the remaining presented the classic onset. Sixteen patients (eight male and eight female, four of whom had the bulbar form) were randomly selected to receive riluzole (Rilutek 50 mg, 1 tablet ϫ 2/day) plus lithium (Carbolithium; two daily 150-mg doses of lithium carbonate), and the remaining (12 male and 16 female, 7 of whom had the bulbar form) received riluzole only (48). In this way, we carefully matched lithium-treated and control patients for bulbar forms and FVC at the time of their inclusion in the study.…”

Section: Geneticmentioning

confidence: 99%

Lithium delays progression of amyotrophic lateral sclerosis

Fornai

Longone

Cafaro

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

504

458

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ALS is a devastating neurodegenerative disorder with no effective treatment. In the present study, we found that daily doses of lithium, leading to plasma levels ranging from 0.4 to 0.8 mEq/liter, delay disease progression in human patients affected by ALS. None of the patients treated with lithium died during the 15 months of the follow-up, and disease progression was markedly attenuated when compared with age-, disease duration-, and sex-matched control patients treated with riluzole for the same amount of time. In a parallel study on a genetic ALS animal model, the G93A mouse, we found a marked neuroprotection by lithium, which delayed disease onset and duration and augmented the life span. These effects were concomitant with activation of autophagy and an increase in the number of the mitochondria in motor neurons and suppressed reactive astrogliosis. Again, lithium reduced the slow necrosis characterized by mitochondrial vacuolization and increased the number of neurons counted in lamina VII that were severely affected in saline-treated G93A mice. After lithium administration in G93A mice, the number of these neurons was higher even when compared with saline-treated WT. All these mechanisms may contribute to the effects of lithium, and these results offer a promising perspective for the treatment of human patients affected by ALS

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Section: Geneticmentioning

confidence: 99%

Lithium delays progression of amyotrophic lateral sclerosis

Fornai

Longone

Cafaro

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

504

458

View full text Add to dashboard Cite

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“…Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is a neuroprotective agent that is the only FDA-approved medication for amyotrophic lateral sclerosis (ALS), although median survival is only prolonged by about 2-3 months (Miller et al, 2007). Two open-label studies support the potential utility of riluzole in treatment-resistant unipolar depression (Zarate et al, 2004a;, and one open-label add-on study found improvements in bipolar depression (Zarate et al, 2005).…”

Section: Riluzole (Major Depressive Disorder and Bipolar Depression)mentioning

confidence: 99%

Novel Drugs and Therapeutic Targets for Severe Mood Disorders

Mathew

Manji

Charney

2008

Neuropsychopharmacol

207

140

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Monoaminergic-based drugs remain the primary focus of pharmaceutical industry drug discovery efforts for mood disorders, despite serious limitations regarding their ability to achieve remission. The quest for novel therapies for unipolar depression and bipolar disorder has generally centered on two complementary approaches: (1) understanding the presumed therapeutically relevant biochemical targets of currently available medications, and using that knowledge to design new drugs directed at both direct biochemical targets and downstream targets that are regulated by chronic drug administration; and (2) developing pathophysiological models of the illness to design therapeutics to attenuate or prevent those pathological processes. This review describes several promising drugs and drug targets for mood disorders using one or both of these approaches. Agents interacting with non-catecholamine neurotransmitter systems with particular promise for unipolar and bipolar depression include excitatory amino acid neurotransmitter modulators (eg, riluzole, N-methyl-D-aspartate antagonists, and AMPA receptor potentiators) and neuropeptide antagonists (targeting corticotropin releasing factor-1 and neurokinin receptors). Potential antidepressant and mood-stabilizing agents targeting common intracellular pathways of known monoaminergic agents and lithium/mood stabilizers are also reviewed, such as neurotrophic factors, extracellular receptor-coupled kinase (ERK) mitogen-activated protein (MAP) kinase and the bcl-2 family of proteins, and inhibitors of phosphodiesterase, glycogen synthase kinase-3, and protein kinase C. A major thrust of drug discovery in mood disorders will continue efforts to identify agents with rapid and sustained onsets of action (such as intravenous administration of ketamine), as well as identify drugs used routinely in non-psychiatric diseases for their antidepressant and mood-stabilizing properties.

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“…Riluzole is another drug in the same class that has been shown to reduce infarct volumes and improve behavioural outcomes in ischaemic injury [124,216] and traumatic brain injury [217,232]. Riluzole is currently indicated for use in ALS [136], but no clinical trials for stroke or traumatic brain injury are currently underway.…”

Section: Glutamate Release Blockersmentioning

confidence: 99%

Glutamate receptors, neurotoxicity and neurodegeneration

Lau¹,

Tymianski²

2010

Pflugers Arch - Eur J Physiol

1,020

697

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Glutamate excitotoxicity is a hypothesis that states excessive glutamate causes neuronal dysfunction and degeneration. As glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), the implications of glutamate excitotoxicity are many and far-reaching. Acute CNS insults such as ischaemia and traumatic brain injury have traditionally been the focus of excitotoxicity research. However, glutamate excitotoxicity has also been linked to chronic neurodegenerative disorders such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease and others. Despite the continued research into the mechanisms of excitotoxicity, there are currently no pharmacological interventions capable of providing significant neuroprotection in the clinical setting of brain ischaemia or injury. This review addresses the current state of excitotoxic research, focusing on the structure and physiology of glutamate receptors; molecular mechanisms underlying excitotoxic cell death pathways and their interactions with each other; the evidence for glutamate excitotoxicity in acute neurologic diseases; laboratory and clinical attempts at modulating excitotoxicity; and emerging targets for excitotoxicity research.

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Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)

Cited by 375 publications

References 28 publications

Lithium delays progression of amyotrophic lateral sclerosis

Lithium delays progression of amyotrophic lateral sclerosis

Novel Drugs and Therapeutic Targets for Severe Mood Disorders

Glutamate receptors, neurotoxicity and neurodegeneration

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