Riluzole
Encyclopedia
Riluzole is a drug
used to treat amyotrophic lateral sclerosis
. It delays the onset of ventilator-dependence or tracheostomy in selected patient
s and may increase survival by approximately 3–5 months.
It is marketed by Sanofi-Aventis
with the brand name
Rilutek.
Riluzole preferentially blocks TTX
-sensitive sodium channels, which are associated with damaged neuron
s. This reduces influx of calcium ion
s and indirectly prevents stimulation of glutamate receptor
s. Together with direct glutamate receptor blockade, the effect of the neurotransmitter
glutamate
on motor neurons is greatly reduced.
However, the action of riluzole on glutamate receptors has been controversial, as no binding of the molecule has been shown on any known receptor. In addition, as its antiglutamate action is still detectable in the presence of sodium channel blockers, it is also uncertain whether or not it acts via this way. Rather, its potent glutamate uptake activator activity seems to mediate many of its effects.
review states a 9% gain in the probability of surviving one year. In secondary analyses of survival at separate time points, there was a significant survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months.
There was a small beneficial effect on both bulbar and limb function, but not on muscle
strength. There were no data on quality of life
, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients.
s such as nausea
and fatigue which lead them to discontinue treatment. Safety monitoring
includes regular liver function tests and people with liver disease
such as hepatitis
should be monitored especially carefully.
In the UK riluzole has been available through the NHS
since 1997 at a standard dosage of 50 mg twice daily. There has been some evidence to show that higher doses might produce more significant improvements in ALS patients but at £5 a tablet it is at risk of being prohibitively expensive given the modest benefit to patients. One study in the Netherlands found that riluzole is metabolised differently by males and females, and its levels in plasma
are decreased in patients who smoke cigarettes or take omeprazole
.
A number of recent case studies
have also indicated that riluzole may have clinical use in mood and anxiety disorder
s. It has been shown to have antidepressant
properties in the treatment of refractory depression
and as an anxiolytic in obsessive-compulsive disorder
and in GAD.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used to treat amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
. It delays the onset of ventilator-dependence or tracheostomy in selected patient
Patient
A patient is any recipient of healthcare services. The patient is most often ill or injured and in need of treatment by a physician, advanced practice registered nurse, veterinarian, or other health care provider....
s and may increase survival by approximately 3–5 months.
It is marketed by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
with the brand name
Brand
The American Marketing Association defines a brand as a "Name, term, design, symbol, or any other feature that identifies one seller's good or service as distinct from those of other sellers."...
Rilutek.
Riluzole preferentially blocks TTX
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...
-sensitive sodium channels, which are associated with damaged neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s. This reduces influx of calcium ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s and indirectly prevents stimulation of glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s. Together with direct glutamate receptor blockade, the effect of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
glutamate
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
on motor neurons is greatly reduced.
However, the action of riluzole on glutamate receptors has been controversial, as no binding of the molecule has been shown on any known receptor. In addition, as its antiglutamate action is still detectable in the presence of sodium channel blockers, it is also uncertain whether or not it acts via this way. Rather, its potent glutamate uptake activator activity seems to mediate many of its effects.
Studies of efficacy
A Cochrane LibraryCochrane Library
The Cochrane Library is a collection of databases in medicine and other healthcare specialties provided by the Cochrane Collaboration and other organisations. At its core is the collection of Cochrane Reviews, a database of systematic reviews and meta-analyses which summarize and interpret the...
review states a 9% gain in the probability of surviving one year. In secondary analyses of survival at separate time points, there was a significant survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months.
There was a small beneficial effect on both bulbar and limb function, but not on muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
strength. There were no data on quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients.
Clinical use
While riluzole has been proven to slow down ALS, patients do not report any subjective improvement. Approximately 10% of patients experience side effectAdverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s such as nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and fatigue which lead them to discontinue treatment. Safety monitoring
Safety monitoring
Safety monitoring of a clinical trial is conducted by an independent physician with relevant expertise. This is accomplished by review of adverse event, immediately after they occur, with timely follow-up through resolution....
includes regular liver function tests and people with liver disease
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
such as hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
should be monitored especially carefully.
In the UK riluzole has been available through the NHS
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
since 1997 at a standard dosage of 50 mg twice daily. There has been some evidence to show that higher doses might produce more significant improvements in ALS patients but at £5 a tablet it is at risk of being prohibitively expensive given the modest benefit to patients. One study in the Netherlands found that riluzole is metabolised differently by males and females, and its levels in plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
are decreased in patients who smoke cigarettes or take omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
.
A number of recent case studies
Case study
A case study is an intensive analysis of an individual unit stressing developmental factors in relation to context. The case study is common in social sciences and life sciences. Case studies may be descriptive or explanatory. The latter type is used to explore causation in order to find...
have also indicated that riluzole may have clinical use in mood and anxiety disorder
Anxiety disorder
Anxiety disorder is a blanket term covering several different forms of abnormal and pathological fear and anxiety. Conditions now considered anxiety disorders only came under the aegis of psychiatry at the end of the 19th century. Gelder, Mayou & Geddes explains that anxiety disorders are...
s. It has been shown to have antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
properties in the treatment of refractory depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and as an anxiolytic in obsessive-compulsive disorder
Obsessive-compulsive disorder
Obsessive–compulsive disorder is an anxiety disorder characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviors aimed at reducing the associated anxiety, or by a combination of such obsessions and compulsions...
and in GAD.
External links
- National Institute for Health and Clinical ExcellenceNational Institute for Health and Clinical ExcellenceThe National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
(NICE) guidelines for prescription of riluzole in the UK http://www.nice.org.uk/page.aspx?o=14491 - Manufacturer's website http://www.rilutek.com/Patients/Default.aspx
- Riluzole (patient information)