Riluzole restores motor activity in rats with post-traumatic peripheral neuropathy

Medico, M.; Nicosia, Angelo; Grech, M.; Onesta, Maria Pia; Sessa, Giuseppe; Rampello, Liborio; Drago, Filippo

doi:10.1016/j.neulet.2003.12.090

Cited by 12 publications

(6 citation statements)

References 18 publications

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“…Regardless of the mechanisms involved, the results suggest that riluzole may have a new role in the promotion of axonal regeneration following peripheral nerve injuries. Consistent with this notion is the recent finding that riluzole can enhance motor activity following peripheral nerve crush injury (Medico et al. , 2004).…”

Section: Discussionsupporting

confidence: 60%

“…Riluzole has a complex pharmacology; it has anaesthetic, analgesic, anti‐ischaemic and anti‐inflammatory properties in addition to its well‐known anti‐excitotoxic properties (Doble, 1996; Gilgun‐Sherki et al. , 2003; Medico et al. , 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Secondly, it may prevent maladaptive structural reorganization from occurring within the CNS. Lastly, riluzole may be beneficial in other situations of peripheral nervous system damage (Medico et al. , 2004), where it may promote regeneration by enhancing axon outgrowth.…”

Section: Introductionmentioning

confidence: 99%

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Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro

Shortland¹,

Leinster²,

White³

et al. 2006

Eur J of Neuroscience

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This study explored the effects of riluzole administration on cell survival and neurite growth in adult and neonatal rat dorsal root ganglion (DRG) neurones in vitro. Neuronal survival was assessed by comparing numbers of remaining neurones in vehicle- and riluzole-treated cultures. A single dose of 0.1 microm riluzole was sufficient to promote neuronal survival in neonatal DRG cultures, whereas repeated riluzole administration was necessary in adult cultures. However, a single administration of riluzole was sufficient to induce neuritogenesis, promote neurite branching and enhance neurite outgrowth in both neonatal and adult DRG cultures. The effects of a single dose of riluzole on adult DRG neurones after peripheral nerve or dorsal root injury were also studied in vitro at 48 h. For both types of injury, riluzole enhanced neurite outgrowth in terms of number, length and branch pattern significantly more on the injured side as compared with the contralateral side. No effect was seen on cell survival. The results suggest that, in addition to its cell survival effects, riluzole has novel growth-promoting effects on sensory neurones in vitro and that riluzole may offer a new way to promote sensory afferent regeneration following peripheral injury.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro

Shortland¹,

Leinster²,

White³

et al. 2006

Eur J of Neuroscience

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“…Based on previous dose-ranging experiments done in our laboratory, phenytoin (administered at 20 mg/kg ip) results in a circulating concentration of ϳ100 M, which is the in vitro dose used. The in vivo dosages are within the therapeutic ranges for humans (33,43,68) and were previously used for animal studies (49,55). Control groups received similar volumes of the drug vehicle, DMSO (8 ml/kg).…”

Section: Methodsmentioning

confidence: 99%

An important functional role of persistent Na⁺current in carotid body hypoxia transduction

Faustino

Donnelly²

2006

Journal of Applied Physiology

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Systemic hypoxia in mammals is sensed and transduced by the carotid body into increased action potential (AP) frequency on the sinus nerve, resulting in increased ventilation. The mechanism of hypoxia transduction is not resolved, but previous work suggested that fast Na(+) channels play an important role in determining the rate and timing of APs (Donnelly, DF, Panisello JM, and Boggs D. J Physiol. 511: 301-311, 1998). We speculated that Na(+) channel activity between APs, termed persistent Na(+) current (I(NaP)), is responsible for AP generation that and riluzole and phenytoin, which inhibit this current, would impair organ function. Using whole cell patch clamp recording of intact petrosal neurons with projections to the carotid body, we demonstrated that I(NaP) is present in chemoreceptor afferent neurons and is inhibited by riluzole. Furthermore, discharge frequencies of single-unit, chemoreceptor activity, in vitro, during normoxia (Po(2) 150 Torr) and during acute hypoxia (Po(2) 90 Torr) were significantly reduced by riluzole concentrations at or above 5 microM, and by phenytoin at 100 microM, without significant affect on nerve conduction time, AP magnitude (inferred from extracellular field), and AP duration. The effect of both drugs appeared solely postsynaptic because hypoxia-induced catecholamine release in the carotid body was not altered by either drug. The respiratory response of unanesthetized, unrestrained 2-wk-old rats to acute hypoxia (12% inspired O(2) fraction), which was measured with whole body plethysmography, was significantly reduced after treatment with riluzole (2 mg/kg ip) and phenytoin (20 mg/kg ip). We conclude that I(NaP) is present in chemoreceptor afferent neurons and serves an important role in peripheral chemoreceptor function and, hence, in the ventilatory response to hypoxia.

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“…Evidence supporting the favorable CNS therapeutic profile of riluzole includes a growing body of work showing that this agent has neuroprotective properties in animal models of brain ischemia [5], spinal cord injury [6, 7], traumatic brain injury [8], Parkinson’s disease [8], post-traumatic peripheral neuropathy [9], and acute noise-induced hearing loss [10]. It has been suggested that inhibition of tyrosine phosphorylation (which is observed in response to brain ischemia) may contribute to riluzole’s neuroprotective properties against excitotoxic injury [11].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Riluzole in psychiatry: a systematic review of the literature

Zarate¹,

Manji²

2008

Expert Opinion on Drug Metabolism & Toxicology

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Background-The glutamate system appears to be an important contributor to the pathophysiology of mood and anxiety disorders. Thus, glutamatergic modulators are reasonable candidate drugs to test in patients with mood and anxiety disorders. Riluzole, a neuroprotective agent with anticonvulsant properties approved for the treatment of amyotrophic lateral sclerosis (ALS) is one such agent.Objective-To assess the potential risks and benefits of riluzole treatment in psychiatric patients.Methods-A PubMed search was performed using the keywords "riluzole", "inhibitor of glutamate release", and "glutamatergic modulator" in order to identify all clinical studies and case reports involving riluzole in psychiatric patients.Results/Conclusion-Riluzole's side effect profile is favorable, and preliminary results regarding riluzole for the treatment of severe mood, anxiety, and impulsive disorders are encouraging.

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Riluzole restores motor activity in rats with post-traumatic peripheral neuropathy

Cited by 12 publications

References 18 publications

Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro

Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro

An important functional role of persistent Na⁺current in carotid body hypoxia transduction

Riluzole in psychiatry: a systematic review of the literature

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Riluzole restores motor activity in rats with post-traumatic peripheral neuropathy

Cited by 12 publications

References 18 publications

Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro

Riluzole promotes cell survival and neurite outgrowth in rat sensory neuronesin vitro

An important functional role of persistent Na+current in carotid body hypoxia transduction

Riluzole in psychiatry: a systematic review of the literature

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An important functional role of persistent Na⁺current in carotid body hypoxia transduction