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Topic: Riluzole

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NMDA

Amyotrophic lateral sclerosis

Motor neurone disease

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Steven Hawking

	Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)
		The results indicate that riluzole 100 mg probably prolongs median survival in patients with amyotrophic lateral sclerosis by two to three months and the safety of the drug is not a major concern.
		To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival.
		Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (P value = 0.042, hazard ratio 0.80, 95% confidence interval 0.64 to 0.99) and there was no evidence of heterogeneity (P value = 0.33).
	www.cochrane.org /reviews/en/ab001447.html (592 words)

	Riluzole - Wikipedia, the free encyclopedia
		Riluzole is a drug used to treat amyotrophic lateral sclerosis.
		Riluzole preferentially blocks TTX-S sodium channels, which are associated with damaged neurons.
		One study in the Netherlands found that riluzole is metabolised differently by males and females, and its levels in plasma are decreased in patients that smoke cigarettes (van Kan et al 2005).
	en.wikipedia.org /wiki/Riluzole (475 words)

	.:: the jack orchard als foundation > current treatments > rilutek ::.
		Riluzole is the first drug to be approved for the treatment of amyotrophic lateral sclerosis (ALS).
		Riluzole is an FDA approved drug for ALS and may be obtained from a medical doctor.
		Riluzole prolongs survival and delays muscle strength deterioration in mice with progressive motor neuronopathy (pmn).
	www.jackorchard.org /2_rilutek.asp (410 words)

	Clinical Trial: Riluzole to Treat Childhood Obsessive-Compulsive Disorder
		Riluzole reduces the activity of glutamate, a neurotransmitter involved in the brain circuitry affected in OCD.
		Riluzole is not related to the selective serotonin reuptake inhibitors (SSRIs) or to the tricyclic antidepressants.
		Riluzole is Food and Drug Administration (FDA)-approved for treatment of amyotrophic lateral sclerosis (ALS), and is currently under investigation at the NIMH for treatment of acute depression.
	www.clinicaltrials.gov /ct/show/NCT00251303?order=1 (1181 words)

	Riluzole, L3
		It is thought that riluzole inhibits the release of glutamate by interfering with sodium (Na+) channels that are required for normal glutamate release.
		Riluzole may disrupt glutamate activity by interfering with the activity of certain proteins involved in the messenger cascade.
		Side effects of riluzole included stiffness, mild increase in blood pressure, and increase in the levels of the enzyme aminotransferase, which sometimes result in elevations of toxic ammonia.
	www.stanford.edu /group/hopes/treatmts/antiglut/l3.html (1486 words)

	TA20 Motor neurone disease - riluzole: Guidance (html)
		In vitro, riluzole inhibits the release of glutamate; decreases firing of motor neurones induced by glutamate receptor agonists and thus protects cells from glutamate-mediated damage.
		Riluzole is contraindicated in the presence of hepatic and/or renal impairment and during pregnancy and breast-feeding.
		It is clear that riluzole is associated with a net increase in costs to the health service, though the magnitude of the increase is difficult to predict accurately.
	www.nice.org.uk /page.aspx?o=14490 (3212 words)

	InteliHealth:
		Riluzole (RIL-yoo-zole) is used to treat patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
		Riluzole is not a cure for ALS, but it may extend survival in the early stages of the disease, and/or may extend the time until a tracheostomy may be needed.
		Riluzole should be taken on a regular basis and at the same time of the day (for example, in the morning and the evening).
	www.intelihealth.com /IH/ihtIH/WSBOS000/408/4631/8557.html?rbrand=Rilutek (633 words)

	Rilutek Prescribing Information - Aventis Pharmaceuticals (Site not responding. Last check: 2007-10-19)
		Riluzole is a white to slightly yellow powder that is very soluble in dimethylformamide, dimethylsulfoxide and methanol, freely soluble in dichloromethane, sparingly soluble in 0.1 N HCl and very slightly soluble in water and in 0.1 N NaOH.
		The metabolism of riluzole is mostly hepatic and consists of cytochrome P450-dependent hydroxylation and glucuronidation.
		The genotoxic potential of riluzole was evaluated in the bacterial mutagenicity (Ames) test, the mouse lymphoma mutation assay in L5178Y cells, the in vitro chromosomal aberration assay in human lymphocytes and the in vivo rat cytogenetic assay and in vivo mouse micronucleus assay in bone marrow.
	www.aventis-us.com /PIs/rilutek_TXT.html (4154 words)

	Rilutek , SPC from the eMC
		Riluzole should be prescribed with care in patients with a history of abnormal liver function, or in patients with slightly elevated serum transaminases (ALT/SGPT; AST/SGOT up to 3 times the upper limit of the normal range (ULN)), bilirubin and/or gamma-glutamyl transferase (GGT) levels.
		The effect of riluzole 50 mg/day was not statistically significant compared to placebo and the effect of 200 mg/day was essentially comparable to that of 100 mg/day.
		Unchanged riluzole is the main component in plasma and is extensively metabolised by cytochrome P450 and subsequent glucuronidation.
	emc.medicines.org.uk /emc/assets/c/html/displaydoc.asp?DocumentID=1672 (1974 words)

	RILUZOLE
		Riluzole is indicated ‘to extend life, or the time to mechanical ventilation, for patients with amyotrophic lateral sclerosis (ALS).’
		Combined results demonstrate that riluzole was associated with a relative reduction in hazard ratio for tracheostomy-free survival at 18 months of 17% (hazard ratio of 0.88, 95% CI 0.75 – 1.02).
		NICE advises that ‘riluzole therapy should be initiated by a neurological specialist with expertise in the management of MND.
	www.keele.ac.uk /depts/mm/MTRAC/ProductInfo/verdicts/R/RILUZOLEv.html (500 words)

	eMJA: Riluzole: a glimmer of hope in the treatment of motor neurone disease
		As riluzole is metabolised hepatically and significant hepatotoxicity occurs in about 0.2% of patients,7 testing liver function monthly for the first 3 months and then at 3 monthly intervals remains important.
		Giving riluzole to patients with advanced disease is problematic, and the current PBS guidelines for authority prescriptions of riluzole stipulate that the date of MND diagnosis (disease duration, ≤ 2 years) and the results of respiratory testing (forced vital capacity, ≥ 60%) must be supplied with the initial authority application.
		Patients need to understand the role of riluzole therapy; specifically, that it is not a cure, but that it has been established to slow the rate of deterioration in muscle function and thereby increase longevity and quality of life.
	www.mja.com.au /public/issues/182_07_040405/kie10062_fm.html (1520 words)

	UCSF Multiple Sclerosis Center
		Riluzole was developed by Sanofi-Aventis for treatment of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrigâs disease, a fatal paralyzing disease with an unknown etiology.
		Riluzole slows neuronal death and as a result, delays the progression of ALS, which is influenced by the death of muscle-controlling nerve cells.
		Riluzole has been approved by the FDA for treatment of ALS, but it is currently not approved by the FDA for treating CIS or MS.
	mscenter.ucsf.edu /research.htm (2480 words)

	Treatment of Patients with ALS: Implications for the Managed Care Pharmacist
		Prescribing riluzole may, therefore, have an effect beyond its physiological one: the psychological status of the patient may be improved, having a further beneficial effect on the patient's physical health.
		Riluzole is most effective in the early stages of ALS30 and should be offered to all patients as early as possible in the disease process to prolong the early, less severe stage of the disease in which the patient has greater capacity to maintain the activities of daily living.
		The provision of riluzole, palliative medications, and supportive care, combined with the ethical issues of mechanical ventilation and end-of-life planning, are aspects of ALS treatment to which the pharmacist and the other members of the team apply their knowledge and experience to improve patient outcomes and quality of life.
	www.amcp.org /data/jmcp/vol4/num6/treatment.html (3777 words)

	Multiple Sclerosis Society Website - Welcome to the MS Society - riluzole
		Riluzole is thought to offer a degree of neuroprotection through preventing the activity of certain molecules involved in damaging nerve fibres.
		Studies of riluzole using animal models of MS have reported significant reductions in disability.
		MRI scans (which produce images of the brain and spinal cord) of people before and after treatment with riluzole, showed reduced loss of nerves in the spinal cord and a reduction in the amount of damage in the brain.
	www.mssociety.org.uk /research/research_explained/riluzole.html (248 words)

	Involvement of Human CYP1A Isoenzymes in the Metabolism and Drug Interactions of Riluzole In Vitro -- Sanderink et al. ...
		Characterization of the CYP isoenzymes responsible for the metabolism of riluzole is of importance in assessing the likelihood
		Standard riluzole samples were prepared in phosphate buffer and mixed with methanol/acetonitrile as for the incubation samples.
		Riluzole glucuronidation was inhibited in a concentration-dependent manner by preincubation with propofol (IC indicating the involvement of the UGT HP4 (UGT1.8/9) isoenzyme
	jpet.aspetjournals.org /cgi/content/full/282/3/1465 (4008 words)

	Bibliography: Rhone-Poulenc Rorer & Basal Gang (Site not responding. Last check: 2007-10-19)
		Riluzole delayed appearance of parkinsonian motor abnormalities in a chronic MPTP monkey model.
		Riluzole pr'events MPTP-induced parkinsonism in the rhesus monkey : a preliminary study.
		Riluzole pretreatment induced a persistent increase in dopamine release may explain the behavioural effects reported with riluzole treatment.
	www.sm.u-bordeaux2.fr /gross/biblio/bibrp.html (735 words)

	RILUZOLE
		Riluzole treatment should be discontinued if ALT levels increase to five times the upper limit of normal.
		Riluzole therapy should be initiated by a neurological specialist with expertise in the management of MND.
		Riluzole is associated with a net increased cost to the health service but the magnitude of this increase is difficult to predict with accuracy.
	www.keele.ac.uk /depts/mm/MTRAC/ProductInfo/summaries/R/RILUZOLEs.html (977 words)

	The Iowa Clinic - Health Library (Site not responding. Last check: 2007-10-19)
		Riluzole is not a cure for ALS, but it may extend survival in the early stages of the disease, and/or may extend the time until a tracheostomy may be needed.
		Although there is no specific information comparing use of riluzole in the elderly with use in other age groups, this medicine has been used in elderly patients and is not expected to cause different side effects or problems in older people than it does in younger adults.
		Riluzole should be taken on a regular basis and at the same time of the day (for example, in the morning and the evening).
	www.iowaclinic.com /controller/ic/micromedex/202792b.htm (894 words)

	CLINICAL REVIEW: Motor Neurone Disease - Part Two - Health - RedOrbit (Site not responding. Last check: 2007-10-19)
		Riluzole is a sodium channel blocker which inhibits the presynaptic release of glutamate among other potentially neuroprotective actions.
		Riluzole is expensive, at about 3,700 per patient per year, but the number of patients requiring the drug is small and they face a lifethreatening disease for which there is no other therapy.
		Riluzole is contraindicated in hepatic or renal impairment and during pregnancy and breast-feeding.
	www.redorbit.com /news/health/474555/clinical_review_motor_neurone_disease__part_two/index.html?source=r_health (2179 words)

	Neuroprotective Agent Riluzole Dramatically Slows Inactivation of Kv1.4 Potassium Channels by a Voltage-Dependent ...
		Riluzole is a neuroprotective agent used in the treatment of the degenerative motor neuron disease ALS (Bensimen et al., 1994
		After recording currents in control saline, cells were superfused with riluzole at concentrations ranging from 1 to 100 µM. A and B, current traces and associated time-dependent plot of bKv1.4 amplitude for cell superfused with increasing concentrations of riluzole as indicated.
		Cheramy A, Barberro L, Godeheu G and Glawinski J (1992) Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in vivo.
	jpet.aspetjournals.org /cgi/content/full/299/1/227 (5268 words)

	amyotrophic lateral sclerosis
		Riluzole, a glutamate antagonist, has been shown to be efficacious in the treatment of patients with amyotrophic lateral sclerosis (ALS) allowing prolonged survival and time to tracheostomy.
		At the present time, riluzole is the only drug for treatment of ALS with demonstrated efficacy in a definitive clinical trial.4,5 This trial showed that riluzole prolongs survival, as well as time to tracheostomy.
		To test the hypothesis that riluzole could benefit UMNs that were sublethally injured by glutamate excitotoxicity, we measured NAA/Cr in the motor cortex of patients with ALS before and after starting riluzole therapy in a non-randomized, open-label study.
	www.mrs.mni.mcgill.ca /mrs/als.html (2505 words)

	Double-Blind Placebo Controlled Trial of Riluzole in Bipolar Depression
		Riluzole is a medication that is used to treat Lou Gehrig’s Disease.
		Riluzole is thought to act by decreasing the release of a brain chemical called glutamate.
		Riluzole has been FDA approved for Lou Gehrig’s Disease, and, therefore, has passed the agency's rigorous safety evaluation process in those patients.
	www.hopkinsmedicine.org /Psychiatry/Moods/riluzole/index.html (1466 words)

	Riluzole detail at IndyaPharma (Site not responding. Last check: 2007-10-19)
		Riluzole is one of the glutamate release inhibitors involved in MPTP toxicity in Parkinson's disease.
		Riluzole is extensively metabolized to six major and a number of minor metabolites, not all of which have been identified.
		Riluzole should be used with caution in elderly patients whose hepatic or renal functions may be compromised due to age.
	www.indyapharma.com /Riluzole-detail.htm (3445 words)

	The Use of Riluzole in the Treatment of Amyotrophic Lateral Sclerosis (Motor Neurone Disease) (Site not responding. Last check: 2007-10-19)
		Riluzole ('Rilutek', Rhone-Poulenc Rorer) is a new drug licensed throughout the European Union and in the United States for use to extend life or the time to mechanical ventilation in patients with ALS.
		On current evidence, riluzole treatment should be limited to those patients most likely to benefit clinically, the selection of whom should be against agreed clinical criteria.
		However, riluzole appears to be relatively safe, which makes the transfer of subsequent prescribing to GPs viable, depending on local policies and arrangements.
	www.shef.ac.uk /uni/academic/R-Z/tiwgap/summs/GN9703.htm (763 words)

	Riluzole (Site not responding. Last check: 2007-10-19)
		Riluzole is not a cure for the disease, but it is the first and currently only drug approved for the treatment of ALS.
		It is not known if riluzole passes into breast milk, but in light of the potentially serious risks to nursing infants, it is recommended that women using this medication refrain from breast feeding.
		Riluzole is generally not prescribed for children; safety and effectiveness for patients in this age group have not been established.
	www.wholehealthmd.com /print/view/1,1560,DR_546,00.html (437 words)

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