Definition
An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.
Description
An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [PubChem]
Top Gene Interactions
Related Pathways
General Information
- Metabolism: No appreciable metabolism, although negligible amounts of an acetyl metabolite have been identified. Amantadine is well absorbed orally from the gastrointestinal tract. The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis. Metabolites are excreted in the urine (A308). Route of Elimination: It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Half Life: Mean half-lives ranged from 10 to 14 hours, however renal function impairment causes a severe increase in half life to 7 to 10 days.
- Uses/Sources: For the chemoprophylaxis, prophylaxis, and treatment of signs and symptoms of infection caused by various strains of influenza A virus. Also for the treatment of parkinsonism and drug-induced extrapyramidal reactions (A308).
- Health Effects: Acute overdosage of amantadine has resulted in cardiac dysfunction (e.g., arrhythmia, tachycardia, hypertension); pulmonary edema and respiratory distress (including adult respiratory distress syndrome); renal dysfunction (e.g., increased BUN, decreased creatinine clearance, renal insufficiency); or CNS toxicity (e.g., insomnia, anxiety, psychotic reactions, lethargy, somnolence, coma). Hyperthermia also has occurred with amantadine overdosage. In addition, seizures may be exacerbated in patients with a history of a seizure disorder (A620).
- Symptoms: Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 2 grams. Drug overdose has resulted in cardiac, respiratory, renal or central nervous system toxicity. Cardiac dysfunction includes arrhythmia, tachycardia and hypertension. Pulmonary edema and respiratory distress (including ARDS) have been reported. Renal dysfunction including increased BUN, decreased creatinine clearance and renal insufficiency can occur. Central nervous system effects that have been reported include insomnia, anxiety, aggressive behavior, hypertonia, hyperkinesia, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucination, psychotic reactions, lethargy, somnolence and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has also been observed in cases where a drug overdose has occurred.
- Treatment: There is no specific antidote for an overdose of Amantadine. However, slowly administered intravenous physostigmine in 1 and 2 mg doses in an adult2 at 1- to 2-hour intervals and 0.5 mg doses in a child3 at 5- to 10-minute intervals up to a maximum of 2 mg/hour have been reported to be effective in the control of central nervous system toxicity caused by amantadine hydrochloride. For acute overdosing, general supportive measures should be employed along with immediate gastric lavage or induction of emesis. Fluids should be forced, and if necessary, given intravenously. The pH of the urine has been reported to influence the excretion rate of Amantadine. (L1744)
- Route of Exposure: Inhalation. Amantadine is well absorbed orally from the gastrointestinal tract.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 800 mg/kg (Oral, Rat) LD50: 700 mg/kg (Oral, Mouse)
- Lethal Dose: The lowest reported acute lethal dose was 2 grams.
Mechanism of Action
Target Name | Mechanism of Action | References |
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Glutamate receptor ionotropic, NMDA 3A Solute carrier family 22 member 2 Multidrug and toxin extrusion protein 1 |
15800186 23241029 9687576 10443547 |
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D(2) dopamine receptor D(1A) dopamine receptor |
The mechanism of its antiparkinsonic effect is not fully understood, but it appears to be releasing dopamine from the nerve endings of the brain cells, together with stimulation of norepinephrine response. The antiviral mechanism seems to be unrelated. The drug interferes with a viral protein, M2 (an ion channel), which is needed for the viral particle to become "uncoated" once it is taken inside the cell by endocytosis. |
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Amantadine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Influenza, Human | 12.93 |
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Short QT Syndrome 1 | 5.66 |
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Virus Diseases | 5.51 |
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Wilms Tumor, Aniridia, Genitourinary Anomalies, Mental Retardation, and Obesity Syndrome | 5.19 |
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Psychosis | 5.17 |
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Candidiasis, Chronic Mucocutaneous | 5.09 |
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Long Qt Syndrome 2 | 4.97 |
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Obesity, Morbid | 4.84 |
|
Congenital central hypoventilation syndrome | 4.64 |
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Cytomegalovirus infection | 4.6 |
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Anorexia nervosa | 4.56 |
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Mycobacterium Infections, Nontuberculous | 4.54 |
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Bulimia nervosa | 4.39 |
|
Mycobacterium Infections | 4.29 |
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Trigeminal Neuralgia | 4.26 |
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TOBACCO ADDICTION, SUSCEPTIBILITY TO | 4.22 |
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Body weight | 3.96 |
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Heroin Dependence | 3.81 |
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Nicotine dependence | 3.71 |
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Gliosis | 3.67 |
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