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Amantadine



Amantadine
Systematic (IUPAC) name
adamantan-1-amine
Identifiers
CAS number 768-94-5
ATC code N04BB01
PubChem 2130
DrugBank APRD00787
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.

Additional recommended knowledge

Contents

Uses

Approved

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).

Off-label uses

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.

Side Effects

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.

Mechanism of its effects

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.

Misuse

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.

Declining effectiveness

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]

References

  1. ^ Hallowell, Edward M. and John J. Ratey, Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder (2005), pp. 253-5.
  2. ^ Endo Pharmaceuticals (May 2003). "Symmetrel (Amantadine) Prescribing Information" (PDF). Retrieved on 2007-08-02.
  3. ^ Cook et al, "Fatal overdose with amantadine". Can. J. Psychiatry (Nov 1986); 31(8), pp. 757-758.
  4. ^ a b Sipress, Alan. "Bird Flu Drug Rendered Useless", Washington Post, 2005-06-18, pp. A01. Retrieved on 2007-08-02. 
  5. ^ 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.

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Amantadine". A list of authors is available in Wikipedia.
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