Riluzole is a medication used to treat amyotrophic lateral sclerosis and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is available in tablet and liquid form. Medical use
Amyotrophic lateral sclerosis
Riluzole was approved in the United States for the treatment of ALS by the U.S. Food and Drug Administration (FDA) in 1995. A Cochrane Library review states a 9% gain in the probability of surviving one year. Adverse effects
Very common (>10% frequency): nausea; weakness; decreased lung function
Common (1–10% frequency): headache; dizziness; drowsiness; vomiting; abdominal pain; increased aminotransferases
Uncommon (0.1-1% frequency): pancreatitis; interstitial lung disease
Rare (<0.1% frequency): neutropenia; allergic reaction (including angiooedema, anaphylactoid reaction)

Overdose
Symptoms of overdose include: neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma and methemoglobinemia. Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue. Contraindications
Contraindications for riluzole include: known prior hypersensitivity to riluzole or any of the excipients inside the preparations, liver disease, pregnancy or lactation. Interactions
CYP1A2 substrates, inhibitors and inducers would probably interact with riluzole, due its dependency on this cytochrome for metabolism. Mechanism of action
Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. Riluzole has also been reported to directly inhibit the kainate and NMDA receptors. The drug has also been shown to postsynaptically potentiate GABAA receptors via an allosteric binding site. However, the action of riluzole on glutamate receptors has been controversial, as no binding of the drug to any known sites has been shown for them.
These are both severe forms of diastolic dysfunction, and patients tend to have advanced heart failure symptoms:
Class III diastolic dysfunction patients will demonstrate reversal of their diastolic abnormalities on echocardiogram when they perform the Valsalva maneuver. This is referred to as "reversible restrictive diastolic dysfunction". Class IV diastolic dysfunction patients will not demonstrate reversibility of their echocardiogram abnormalities, and are therefore said to have "fixed restrictive diastolic dysfunction".The presence of either class III and IV diastolic dysfunction is associated with a significantly worse prognosis. These patients will have left atrial enlargement, and many will have a reduced left ventricular ejection fraction that indicates a combination of systolic and diastolic dysfunction.Imaged volumetric definition of systolic heart performance is commonly accepted as ejection fraction. Volumetric definition of the heart in systole was first described by Adolph Fick as cardiac output. Fick may be readily and inexpensively inverted to cardiac output and ejection fraction to mathematically describe diastole. Decline of ejection fraction paired with decline of E/A ratio seems a stronger argument in support of a mathematical definition of diastolic heart failure.Another parameter to assess diastolic function is the E/E ratio, which is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E). Diastolic dysfunction is assumed when the E/E ratio exceed 15.Newer echocardiographic techniques such as speckle tracking for strain measurement, particularly for the left atrium, are becoming increasingly utilised for the diagnosis of HFpEF. Treatment
Despite increasing incidence of HFpEF effective inroads to therapeutics have been largely unsuccessful.