INFLUENZA INFECTIONS OF MICE: II. CURATIVE ACTIVITY OF α‐METHYL‐1‐ADAMANTANEMETHYLAMINE HCl (RIMANTADINE HCl)

1-β- d -Ribofuranosyl-1,2,4-triazole-3-carboxamide (Virazole) was found to possess significant antiviral activity against aerosol-induced or intranasally induced influenza A 0 , A 2 , and B virus infections in mice. Significant protection was achieved by both oral and intraperitoneal routes of administration. Depending upon the level of virus infection, antiviral activity was best observed at the daily dose of 75 mg/kg. The efficacy of the compound was evidenced by an increase in survivor number, prolongation of mean survival time, suppression of lung consolidation, or decrease in hemagglutinin titer in the infected lung samples. The therapeutic value of this synthetic triazole nucleoside was evident as noted by a significant increase in survivor number even if the treatment was started as late as 24 h after infection with an aerosol of influenza A 2 virus.

Section: Resultsmentioning

confidence: 99%

Suppression by 1-β- d -Ribofuranosyl-1,2,4-Triazole-3-Carboxamide (Virazole, ICN 1229) of Influenza Virus-Induced Infections in Mice

Khare¹,

Sidwell²,

Witkowski³

et al. 1973

“…This drug has the same antiviral spectrum and mode of action as its structural analogue amantadine hydrochloride (11). Both amantadine hydrochloride and rimantadine hydrochloride have therapeutic activity when given orally 48 to 72 h after infection (2,4,10,11). Grunert et al (4) reported that amantadine hydrochloride was effective by the aerosol route, but only within 1 h after infection.…”

mentioning

confidence: 99%

“…Rimantadine hydrochloride (a-methyl-1-adamantanemethylamine hydrochloride; E. I. duPont de Nemours and Co., Inc., Newark, N.J.) has been reported to be active against influenza A infections in tissue culture, animals, and man (11,18,19). This drug has the same antiviral spectrum and mode of action as its structural analogue amantadine hydrochloride (11).…”

mentioning

confidence: 99%

Treatment of Influenza Infection of Mice by Using Rimantadine Hydrochlorides by the Aerosol and Intraperitoneal Routes

Stephen

Dominik

Moe

et al. 1975

Rimantadine hydrochloride was administered for 4 days in a small-particle (95% < 6.5 μm) aerosol (8.8 mg/kg per day) or intraperitoneally (40 mg/kg per day) to mice previously infected with influenza A/Aichi/2/68 (H 3 N 2 ), mouse adapted. Mean time to death and incidence of survival were significantly increased in all treated groups of mice. The rate of eventual disappearance of virus from lung tissue was also accelerated by therapy. However, maximal mean virus titer per lung, and lung histopathology, did not reveal any difference between control and either group of treated mice. Aerosol therapy initiated at 72 h postinfection was as effective as that initiated at 6 h, even though lung virus titers of these mice had already peaked by 72 h. In contrast, intraperitoneal therapy initiated at 72 h was not effective in all studies.

“…The singledose oral 50% lethal dose of these drugs for mice has been estimated to be 700 mg of amantadine per kg (14), 739 mg of rimantadine per kg (C. E. Hoffman, personal communication), and 6,400 mg of ribavirin per kg (R. W. Sidwell, personal communication). For the present study, the drugs were dissolved at a concentration of 0.25 mg/ml in sterile distilled water and given to the appropriate groups of mice in lieu of drinking water as previously described by McGahen et al (9). New stock solutions were prepared weekly, and fresh drug solution was added to the drinking vessels daily.…”

Section: And Methodsmentioning

confidence: 99%

“…Amantadine, rmantadine, and ribavirin have demonstrated activity against disease caused by several strains of type A influenza virus (6,8,9,12,13). This paper reports results of studies on the efficacy of these three drugs given by the oral route for the prevention and/or treatment of type A/New Jersey (swine) influenza virus infections in mice.…”

mentioning

confidence: 99%

Activity of Amantadine, Rimantadine, and Ribavirin Against Swine Influenza in Mice and Squirrel Monkeys

Scott

Stephen

Berendt

1978

Amantadine, rimantadine, and ribavirin given orally, either prophylactically or therapeutically, reduced mortality and increased the survival time of 3-week-old mice infected with the type A/New Jersey/8/76 (swine) strain of influenza virus. In addition, amantadine and rimantadine, administered therapeutically, increased the rate of virus clearance from lungs of infected mice. Administration of amantadine either before or after virus challenge ameliorated the illness in squirrel monkeys; when administered therapeutically, it appeared to eliminate virus shedding from infected monkeys within hours after therapy was initiated.