Amantadine

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Image:Amantadine.png
Amantadine
Systematic (IUPAC) name
adamantan-1-amine
Identifiers
CAS number	768-94-5
ATC code	N04 BB01
PubChem	9036
DrugBank	APRD00787
Chemical data
Formula	C₁₀H₁₇N
Mol. weight	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-amino adamantane, sold as Symmetrel®) is an antiviral drug that was approved by the Food and Drug Administration in 1976 for the treatment of Influenzavirus A in adults. The drug has also been demonstrated to help reduce symptoms of Parkinson's disease and drug-induced extrapyramidal syndromes. 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). Amantadine has been shown to relieve SSRI-induced anorgasmia in some people, though not in all people. There have been anecdotal reports that low-dose amantadine has been successfully used to treat ADHD.<ref>Hallowell and Ratey, Delivered from Distraction: Getting the Most out of Life with Attention Deficit Disorder (2005), pp. 253-5.</ref>

It is a derivate of adamantane, like a similar drug rimantadine.

1 Mechanism of its effects
2 Side Effects
3 Misuse
4 Declining effectiveness
5 See also
6 External links
7 Notes

[edit] 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 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.

[edit] Side Effects

Amantadine has been associated with several CNS 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. This is due to the fact that Amantadine possesses significant anticholinergic activity.

[edit] Misuse

Recently, amantadine is reported to have been used in China poultry farming in an effort to protect the birds against avian flu. 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. 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.

[edit] 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]

[edit] See also

[edit] External links

[edit] Notes

Link page to external chemical sources.

Antivirals (primarily J05A, also S01AD and D06BB) edit

Anti-herpesvirus agents		Aciclovir, Cidofovir, Docosanol, Famciclovir, Fomivirsen, Foscarnet, Ganciclovir, Idoxuridine, Penciclovir, Trifluridine, Tromantadine, Valaciclovir, Valganciclovir, Vidarabine
Anti-influenza agents		Amantadine, Oseltamivir, Peramivir, Rimantadine, Zanamivir

Antiretroviral drugs	NRTIs	Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine
	NtRTIs	Tenofovir
	NNRTIs	Efavirenz, Delavirdine, Nevirapine
	PIs	Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir
	Fusion inhibitors	Enfuvirtide

Other antiviral agents		Adefovir, Fomivirsen, Imiquimod, Inosine,Interferon, Podophyllotoxin, Ribavirin, Viramidine