Amantadine

spinqualitylabelsall models Amantadine, also known as Symmetrel Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Better Known as: Symmetrel

• Marketed By: Endo Pharmaceuticals
• Major Indication: Influenza Infection
• Drug Class: M2 Proton Channel Inhibitor
• Date of FDA Approval (Patent Expiration): 1966 (1986)
• 1994 Sales: N/A
• Importance: One of the the first treatments approved by the FDA and the first approved for treatment of Influenza Infections. Nearly 100% of influenza viruses had developed resistance to rimantadine, and it is no longer recommended as a treatment for the flu. Interestingly, in 1969 it was also discovered that Amantadine helped reduce the symptoms of Parkinson's Disease.
• The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information

Mechanism of Action

The Influenza A Virus viral envelope is dotted with various ion channels including M2 Proton Channels. The plays a critical role in the life cycle of the Influenza virus. It enables hydrogen ions to enter the virion form the endosome. The result of this is a more acidic environment within the virus, causing dissociation of the viral matrix protein M1 from the ribonucleoprotein RNP. Dissociation of the viral matrix protein is a crucial step in uncoating of the virus and exposing its contents to the cytoplasm of the host cell, allowing the virus to hijack the cellular machinery to replicate. formed by the M2 protein, utilizing Val 27, Ala 30 and Ser 31 in each M2 protein chain, effectively disabling the protein from transferring protons into the viral particle.

Pharmacokinetics

M2 Proton Channel Inhibitor Pharmacokinetics
Parameter	Rimantadine	Amantadine
Tmax (hr)	4.3	2.5
Cmax (ng/ml)	310	402
Bioavailability (%)	>90	>90
Protein Binding (%)	40	67
T1/2 (hr)	27.7	~15
AUC (ng/ml/hr)	11917	5420
Dosage (mg)	100	100
Metabolism	Negligible	Negligible