Antiviral agents rimantadine

Pharmacology Rimantadine is a synthetic antiviral agent that appears to exert its... 

Viral resistance develops rapidly in approximately 30% of individuals treated with amantadine or rimantadine. Resistant viruses are associated with the failure of drug prophylaxis in close contacts of infected individuals who have been treated with these antiviral agents. Mutation in the transmembrane domain of the M2 protein is the most frequent cause of resistance to amantadine and rimantadine. 

In many viral infections the clinical symptoms appear late in the course of the disease at a time when most of the virus particles have replicated. [Note This contrasts with bacterial diseases in which the clinical symptoms are usually coincident with bacterial proliferation.] At this late, symptomatic stage of the viral infection, administration of drugs that block viral replication have limited effectiveness. However, some antiviral agents are useful as prophylactic agents. For example, amantadine [a MAN ta deen] and its congener, rimantadine [rih MAN ta deen] have been shown to be equally effective in preventing influenza A infections. [Note Amantadine is also effective in the treatment of some cases of Parkinson s disease (see p. 87).]... 

Immunoprophylaxis with inactivated vaccine remains the principal means for reducing influenza-related morbidity and death. Although the vaccine provides the best protection against influenza, there are four antiviral agents that are used to prevent or treat influenza amantadine, rimantadine, zanamivir, and oseltamivir. To shorten the duration of influenza symptoms, all agents should be initiated within 2 days of onset of symptoms. 

Amantadine hydrochloride [665-66-7] (1-adamantanamine hydrochloride, 41), C qH N HQ., (93) is a good example of a narrow-spectmm agent active only against influenza A vims. It became the first antiviral dmg available for systemic use in the United States when it was approved by the FDA in 1966 for use against Asian influenza. In 1976, FDA approval was extended to the use of amantadine for the reHef of symptoms of all influenza A strains. Amantadine is marketed by Du Pont de Nemours Co., Inc. A stmcturaHy related dmg, rimantadine hydrochloride [1501 -84-4] C 2H2 N HQ, (a-methyl-l-adamantanemethylamine hydrochloride, 42), is widely used in Russia to treat influenza A vims (94). 

The Centers for Disease Control s (CDC) Immunization Practices Advisory Committee recommends annual vaccination as the method of choice in the prevention of influenza infection. However, when vaccination is contraindicated or early vaccination is not possible, amantadine and rimantadine are effective prophylactic agents that have been shown to protect approximately 70 to 90% of patients from influenza A infection. Since these drugs do not prevent the host immune response to influenza A, they may be used to prevent infection during the 2- to 4-week period required to develop immunity following vaccination. An additional use of amantadine, unrelated to its antiviral activity, is in the therapy of Parkinson s disease (see Chapter 31). 

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