An effective anti-influenzavirus combination of mopyridone and rimantadine hydrochloride

Galabov, Angel S.; Uzunov, S.; Tancheva, Lyubka; Velichkova, E; Hadjiathanassova, V.; Behar, Moisés

doi:10.1016/0166-3542(91)90269-w

Cited by 3 publications

(6 citation statements)

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“…The first study on the combination of specific influenza virus replication inhibitors used rimantadine plus mopyridone (which targeting M1 protein of influenza A virus) and showed a synergistic effect (Galabov et al, 1991(Galabov et al, , 1994a. It was followed by investigations on the effect of combinations with neuraminidase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

“…The first study on the combination of specific influenza virus replication inhibitors used rimantadine plus mopyridone (which targeting M1 protein of influenza A virus) and showed a synergistic effect (Galabov et al, 1991(Galabov et al, , 1994a (Madren et al, 1995). Peramivir and ribavirin produce an additive to synergistic effect against influenza A virus in vitro and in experimental influenza virus A (H1N1) infection in mice (Smee et al, 2002).…”

Section: Some Authors Noticed a More Rapid Development Of Resistancmentioning

confidence: 99%

“…The character of the combined antiviral effect of rimantadine hydrochloride and oseltamivir in influenza virus A (H3N2) infection in mice was determined according to the threedimensional model (Prichard and Shipman, 1990) for analysis of drug-drug interactions, modified for in vivo trials (Nikolaeva and Galabov, 2000 (Ilyenko et al, 1972;Galabov et al, 1991), and 1 mg/kg of oseltamivir as registered against A/Victoria/3/75(H3N2) and A/Shandong/09 /93(H3N2) (Sidwell et al, 1998). The results summarized in Table 1 Figure 2.…”

Section: Combination Activity Effectmentioning

confidence: 99%

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Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Galabov

Simeonova

Gegova

2006

Antivir Chem Chemother

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We studied the combination effect of rimantadine hydrochloride and oseltamivir phosphate on mice infected with influenza A/Aichi/2/68 (H3N2) virus. Compounds were simultaneously administered in a 5-day-treatment course, starting 4 h before intranasal infection with 10 or 20 viral 50% mouse lethal doses. Initially, we tested combinations of oseltamivir (0.05, 0.1 and 0.2 mg/kg/day) and rimantadine (2.5, 5.0 and 7.5 mg/kg/day). Significant differences were recorded between combinationtreated groups, and groups with separately applied compounds and the placebo group, such as: protection index of oseltamivir with 5.0 or 7.5 mg/kg rimantadine varied between 34-41% and 43-87%, respectively, whereas the individual effects of oseltamivir, 5 mg/kg of rimantadine and 7.5 mg/kg of rimantadine were 0-10%, 0% and 18.7-29.6%, respectively; mean survival time in combination-treated groups was lengthened by 3.1-6.9 days, in oseltamivir groups by 0-1.9 days, and in rimantadine groups by 0.8-1.3 days at 5 mg/kg and 2.6-3.2 days at 7.5 mg/kg. The threedimensional method of Prichard and Shipman characterized the combination effect as synergistic. Further, we studied the activity of 0.05 mg/kg/day of oseltamivir combined with 5 mg/kg of rimantadine. Lung virus titre in Madin Darby canine kidney cells, lung index and consolidation score proved the high effectiveness of the combination. When compared with the placebo group, a 2.8 log 10 lower titre of 50% cell culture infectious dose (CCID 50 ) was recorded in the combinationtreated group at 48-60 h post-infection (the peak of lung virus growth). This is in contrast to the 0.1-1.0 log 10 and 1.1-1.4 log 10 reduction in CCID 50 titre observed in the oseltamivir and rimantadine groups, respectively. These data emphasize the high anti-influenza A potential of the combination.

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Section: Introductionmentioning

confidence: 99%

“…The first study on the combination of specific influenza virus replication inhibitors used rimantadine plus mopyridone (which targeting M1 protein of influenza A virus) and showed a synergistic effect (Galabov et al, 1991(Galabov et al, , 1994a (Madren et al, 1995). Peramivir and ribavirin produce an additive to synergistic effect against influenza A virus in vitro and in experimental influenza virus A (H1N1) infection in mice (Smee et al, 2002).…”

Section: Some Authors Noticed a More Rapid Development Of Resistancmentioning

confidence: 99%

Section: Combination Activity Effectmentioning

confidence: 99%

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Rimantadine and Oseltamivir Demonstrate Synergistic Combination Effect in an Experimental Infection with Type a (H3N2) Influenza Virus in Mice

Galabov

Simeonova

Gegova

2006

Antivir Chem Chemother

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show abstract

“…The first study of the combination of specific influenza virus replication inhibitors was on rimantadine plus mopyridone (targeting M1 protein of influenza A virus) and it showed a synergistic effect (21) against H3N2 virus in cell cultures. Zanamivir with 2-FDG demonstrated additive effect in cells (50).…”

Section: Other Combination Therapiesmentioning

confidence: 99%

“…2I) which showed antiviral effect in vitro and in vivo against influenza А (Н1N1, Н2N2, Н3N2, Н7N7) and B type. Mopyridone alters the contact of M1 protein with the lipid bilayer of the envelope and thus interrupts the morphogenesis and assembly of the viral particles (20,23,86).…”

Section: м1 Inhibitorsmentioning

confidence: 99%