Rimantadine
Encyclopedia
Rimantadine is an orally administered antiviral drug
used to treat, and in rare cases prevent, influenzavirus A
infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug amantadine
are derivates of adamantane
. Rimantadine was approved by the Food and Drug Administration
(FDA) in 1994.
According to the CDC, 100% of seasonal H3N2 and 2009 pandemic flu samples tested have shown resistance to rimantadine and it is no longer recommended to prescribe for treatment of the flu.
, Delaware
(US patent on new chemical compound № 3352912, 1965 and on the first method of synthesis № 3592934, 1967). Prichard's methods of synthesis of rimantadine from the corresponding ketone oxime were based on its reduction with lithium aluminum hydride.
, an ion channel
specified by virion M2 gene
, plays an important role in the susceptibility of influenza A virus to inhibition by rimantadine. Resistance to rimantadine can occur as a result of an amino acid substitutions at certain locations in the transmembrane region of M2. This prevents binding of the antiviral to the channel.
Rimantadine, like its antiviral cousin amantadine
, possesses some NMDA antagonistic
properties and is used as an antiparkinsonic drug (i.e., in the treatment of Parkinson's disease
). However, neither rimantadine nor amantadine are preferred agents for this therapy and are generally reserved for cases of the disease which are less responsive to front-line treatments.
(acetaminophen e.g. Tylenol
) or acetylsalicylic acid (aspirin) while taking rimantadine is known to reduce the body's uptake of rimantadine by approximately 12%. Cimetidine
also affects the body's uptake of rimantadine.
adverse effects
. Approximately 6% of patients (compared to 4% of patients taking a placebo) reported side effects at a dosage of 200 mg/d. Common side effects include:
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
used to treat, and in rare cases prevent, influenzavirus A
Influenzavirus A
Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
are derivates of adamantane
Adamantane
Adamantane is a colorless, crystalline chemical compound with a camphor-like odor. With a formula C10H16, it is a cycloalkane and also the simplest diamondoid. Adamantane molecules consist of three cyclohexane rings arranged in the "armchair" configuration. It is unique in that it is both rigid...
. Rimantadine was approved by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) in 1994.
According to the CDC, 100% of seasonal H3N2 and 2009 pandemic flu samples tested have shown resistance to rimantadine and it is no longer recommended to prescribe for treatment of the flu.
History
Rimantadine was discovered in 1963 and patented in 1965 in the USA by William W. Prichard in Du Pont & Co., WilmingtonWilmington, Delaware
Wilmington is the largest city in the state of Delaware, United States, and is located at the confluence of the Christina River and Brandywine Creek, near where the Christina flows into the Delaware River. It is the county seat of New Castle County and one of the major cities in the Delaware Valley...
, Delaware
Delaware
Delaware is a U.S. state located on the Atlantic Coast in the Mid-Atlantic region of the United States. It is bordered to the south and west by Maryland, and to the north by Pennsylvania...
(US patent on new chemical compound № 3352912, 1965 and on the first method of synthesis № 3592934, 1967). Prichard's methods of synthesis of rimantadine from the corresponding ketone oxime were based on its reduction with lithium aluminum hydride.
Clinical usage
Rimantadine is believed to inhibit influenza's viral replication, possibly by preventing the uncoating of the virus's protective shells, which are the envelope and capsid. Genetic studies suggest that the virus M2 proteinM2 protein
The M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer , where the units are helices stabilized by two disulfide bonds...
, an ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
specified by virion M2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, plays an important role in the susceptibility of influenza A virus to inhibition by rimantadine. Resistance to rimantadine can occur as a result of an amino acid substitutions at certain locations in the transmembrane region of M2. This prevents binding of the antiviral to the channel.
Rimantadine, like its antiviral cousin amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
, possesses some NMDA antagonistic
NMDA receptor antagonist
NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
properties and is used as an antiparkinsonic drug (i.e., in the treatment of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
). However, neither rimantadine nor amantadine are preferred agents for this therapy and are generally reserved for cases of the disease which are less responsive to front-line treatments.
Drug interactions
Taking paracetamolParacetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
(acetaminophen e.g. Tylenol
Tylenol
Tylenol is a North American brand of drugs advertised for reducing pain, reducing fever, and relieving the symptoms of allergies, cold, cough, and flu. The active ingredient of its original, flagship product, paracetamol , is marketed as an analgesic and antipyretic...
) or acetylsalicylic acid (aspirin) while taking rimantadine is known to reduce the body's uptake of rimantadine by approximately 12%. Cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
also affects the body's uptake of rimantadine.
Possible side effects
Rimantadine can produce gastrointestinal and central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
adverse effects
Adverse effect (medicine)
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...
. Approximately 6% of patients (compared to 4% of patients taking a placebo) reported side effects at a dosage of 200 mg/d. Common side effects include:
- nauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
- upset stomach
- nervousness
- tiredness
- lightheadedness
- trouble sleeping
- difficulty concentrating