Author: GASPARINI, R.; AMICIZIA, D.; LAI, PL.; BRAGAZZI, NL.; PANATTO, D.
Title: Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: influenza life-cycle and currently available drugs Document date: 2014_9_23
ID: 5td3lhlf_29
Snippet: Amantadine and Rimantadine (Figs. 2, 3) were the first generation of influenza antiviral agents [203] . Amantadine (1-aminoadamantane) is a derivative of the hydrocarbon tricyclo[3.3.1.1.3,7]decane. Amantadine can be administered either as a hydrochloride derivative (Symmetrel), as 100 mg tablets or syrup, or as its effective derivative Rimantadine (α-methyl-1adamantanemethylamine hydrochloride, Flumadine). At high concentrations, Amantadine and.....
Document: Amantadine and Rimantadine (Figs. 2, 3) were the first generation of influenza antiviral agents [203] . Amantadine (1-aminoadamantane) is a derivative of the hydrocarbon tricyclo[3.3.1.1.3,7]decane. Amantadine can be administered either as a hydrochloride derivative (Symmetrel), as 100 mg tablets or syrup, or as its effective derivative Rimantadine (α-methyl-1adamantanemethylamine hydrochloride, Flumadine). At high concentrations, Amantadine and Rimantadine nonspecifically raise the pH within cellular endosomes, thus inhibiting or retarding the acid-induced conformational change in viral HA. At low concentrations, Amantadine and Rimantadine specifically inhibit the ion-channel activity of the M2 protein [204] . Crossing the brain-blood barrier and being present in the cerebrospinal fluid (CSF) with a concentration around 75% of serum level, Amantadine can also be used to treat Parkinson's disease [205] , depression and obsessivecompulsive disorder (OCD) [206] , Huntington's disease [207] , attention deficit hyperactivity disorder (AD-HD) and other neuropsychiatric diseases [208] , cocaine abuse and dependence [209] , HCV [210] , Creutzfeldt-Jakob's disease [211] , Borna's disease [212] , herpes and post herpes zoster neuralgia (PHN) [213] . This variety of uses seems to suggest that Amantadine, besides blocking the M2 channel, acts on an array of receptors, from the dopaminergic receptors to noradrenergic, serotoninergic, cholinergic, and N-Methyl-Daspartate (NMDA) receptors [214, 215] . After being rapidly adsorbed, with an excellent bioavailability profile (usually in the range 86-94%) [216] , the drug reaches peak plasma levels within 4 hours [216] . The plasma elimination half-life is about 11-15 h in patients with normal renal function. It has a plasma protein binding of about 67% [216] .
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