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Amantadine
From Wikipedia, the free encyclopedia
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Amantadine
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| Systematic (IUPAC) name | |
| adamantan-1-amine | |
| Identifiers | |
| CAS number | |
| ATC code | N04 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C10H17N |
| Mol. mass | 151.249 g/mol |
| Pharmacokinetic data | |
| Bioavailability | well absorbed |
| Protein binding | approx 67% |
| Metabolism | negligible |
| Half life | 10-14 hours, in renal impairment up to 7-10 days |
| Excretion | renal |
| Therapeutic considerations | |
| Pregnancy cat. |
C |
| Legal status | |
| Routes | oral |
Amantadine (1-aminoadamantane, sold as Symmetrel) is an antiviral drug used both as an antiviral and an antiparkinsonic.
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It was approved by the Food and Drug Administration in 1976 for the treatment of Influenzavirus A in adults. In 1969 the drug was also discovered by accident to help reduce symptoms of Parkinson's disease and drug-induced extrapyramidal syndromes. It is a derivative of adamantane, like rimantadine, a similar drug.
As an antiparkinsonic it can be used as monotherapy; or together with L-DOPA to treat L-DOPA-related motor fluctuations (i.e., shortening of L-DOPA duration of clinical effect, probably related to progressive neuronal loss) and L-DOPA-related dyskinesias (choreiform movements associated with long-term L-DOPA use, probably related to chronic pulsatile stimulation of dopamine receptors).
There have been anecdotal reports, based on research by Dr. William Singer of Harvard University, that low-dose amantadine has been successfully used to treat ADHD.[1] Amantadine has been shown to relieve SSRI-induced anorgasmia in some people, though not in all people.
Amantadine has been associated with several central nervous system side effects, including nervousness, anxiety, agitation, insomnia, difficulty in concentrating, and exacerbations of pre-existing seizure disorders and psychiatric symptoms in patients with schizophrenia or Parkinson's disease. These side effects are likely due to amantadine's dopaminergic and adrenergic activity, and to a lesser extent, its activity as an anticholinergic.
Cases of suicidal ideation in patients treated with amantadine have been described,[2] although this psychiatric adverse event is relatively rare. Nonetheless, clinical surveillance of suicidal ideation in patients on amantadine is warranted at the clinician's discretion, as amantadine has been implicated as the major fatal (biologically toxic) factor in completed patient suicides.[3]
Another potential side effect is livedo reticularis, a dermatological reaction that results in skin mottling and purpurish mesh network of blood vessels.
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. Furthermore, it appears to be a weak NMDA receptor antagonist and an anticholinergic.
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.
Recently, amantadine is reported to have been used in China poultry farming in an effort to protect the birds against avian influenza.[4] In western countries and according to international livestock regulations, amantadine is approved only for use in humans. Chickens in China have received an estimated 2.6 billion doses of amantadine.[4] Avian flu (H5N1) strains in China and southeast Asia are resistant to amantadine, but strains circulating elsewhere seem to be sensitive. If amantadine resistant strains of the virus spread, the drug of choice in an avian flu outbreak will likely be restricted to one of the scarcer and costlier oseltamivir or zanamivir, which work by a different mechanism and are less likely to trigger resistance.
Early in the 2005/2006 flu season, the United States' Center for Disease Control [CDC] found rates of amantadine resistance to be much higher than in previous seasons. Looking at samples from 26 states yielded the following findings:
A total of 193 (92.3%) of 209 influenza A(H3N2) and 2 (25%) of 8 influenza A(H1N1) viruses analyzed contained point mutations resulting in a serine-to-asparagine change at amino acid 31 (S31N) of the M2 protein that conferred adamantane resistance. [1]
A resistance rate of 92% for the major flu strain was called "alarmingly high". The CDC issued an alert to doctors not to prescribe amantadine any more for the season.[2] Among some Asian countries, A/H3N2 and A/H1N1 resistance has reached 100%.[5]
- ^ Hallowell, Edward M. and John J. Ratey, Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder (2005), pp. 253-5.
- ^ Endo Pharmaceuticals (May 2003). "Symmetrel (Amantadine) Prescribing Information" (PDF). Retrieved on 2007-08-02.
- ^ Cook et al, "Fatal overdose with amantadine". Can. J. Psychiatry (Nov 1986); 31(8), pp. 757-758.
- ^ a b Sipress, Alan. "Bird Flu Drug Rendered Useless", Washington Post, 2005-06-18, pp. A01. Retrieved on 2007-08-02.
- ^ Deyde, Varough M.; Xu, Xiyan; Bright, Rick A.; Shaw, Michael; Smith, Catherine B.; Zhang, Ye; Shu, Yuelong; Gubareva, Larisa V.; Cox, Nancy J.; Klimov, Alexander I. (2007-07-15). "Surveillance of Resistance to Adamantanes among Influenza A(H3N2) and A(H1N1) Viruses Isolated Worldwide". Journal of Infectious Diseases 196 (2): 249-257. Retrieved on 2007-08-02.
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| Dopa and derivatives | Levodopa, Melevodopa, Etilevodopa |
| Adamantane derivatives | Amantadine |
| Dopamine agonists | Apomorphine, Bromocriptine, Cabergoline, Dihydrexidine, Dihydroergocryptine mesylate, Fenoldopam, Lisuride, Pergolide, Piribedil, Pramipexole, Quinpirole, Ropinirole, Rotigotine, SKF 38393, SKF 82958 |
| MAOIs | Selegiline, Rasagiline |
| Other | Tolcapone, Entacapone, Budipine |
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|---|---|
| Anti-herpesvirus (DNA, I) | guanine analogues (Aciclovir, Famciclovir, Ganciclovir, Penciclovir, Valaciclovir, Valganciclovir) • nucleoside analogues (Idoxuridine, Trifluridine, Vidarabine) • Cidofovir • Docosanol • Fomivirsen • Foscarnet • Tromantadine |
| HPV/MC (DNA, I) | Imiquimod • Podophyllotoxin |
| Hepatitis B (DNA, VII) | Adefovir dipivoxil • Interferon alfa-2b • Pegylated interferon alfa-2a • Lamivudine • Entecavir • Telbivudine • Tenofovir† |
| Hepatitis C (RNA, IV) | Ribavirin • Taribavirin |
| Picornavirus (RNA, IV) | Pleconaril |
| Anti-influenza agents (RNA, V) | Arbidol
adamantane derivatives/M2 inhibitors (Amantadine, Rimantadine) neuraminidase inhibitors (Oseltamivir, Peramivir†, Zanamivir) |
| HIV (Reverse, VI) | See HIV pharm |
| Other antiviral agents | general (Inosine, Interferon) |
| †Undergoing clinical trials, not FDA approved. | |
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| Influenza | Research - Vaccine - Avian influenza - Treatment - Genome sequencing - Season |
| Influenza viruses | Orthomyxoviridae - Influenza A - Influenza B - Influenza C |
| Subtypes of Influenza A virus | H1N1 - H1N2 - H2N2 - H3N2 - H3N8 - H5N1 - H5N2 - H5N3 - H5N8 - H5N9 - H7N1 - H7N2 - H7N3 - H7N4 - H7N7 - H9N2 - H10N7 |
| H5N1 | Genetic structure - Transmission and infection - Global spread - Clinical Trials - Human mortality |
| Antiviral drugs | Arbidol - adamantane derivatives (Amantadine, Rimantadine) - neuraminidase inhibitors (Oseltamivir, Peramivir, Zanamivir) Experimental (Peramivir) |
| Influenza vaccines | FluMist - Fluzone |
| Influenza pandemics | Asian Flu - Hong Kong Flu - Spanish flu - Fujian flu - Pandemic Severity Index |
| Influenza in non-human mammals | Canine influenza - Equine influenza - Swine flu |