Prevention of death in mice infected with coxsackievirus A16 using guanidine HCl mixed with substituted benzimidazoles.
A significant reduction in the death rate of infant mice infected with ten 50% lethal doses (LD50) of coxsackievirus A16 was observed when they were treated 58 h after infection with two injections of guanidine at 145 mg/kg per injection. Tremors occurred at this level but disappeared after treatment was discontinued. Tremors were apparent, but less severe at 97 mg/kg per injection and did not occur at 48 mg/kg per injection. No antiviral effect could be detected at either of these levels of guanidine. When an inactive level of guanidine (97 mg/kg per injection) was combined with 1.7 mg/kg per injection of LY122771-72, LY127123, or 2-(alpha-hydroxybenzyl)benzimidazole (HBB) and 17 mg/kg per injection of 2-guanidino-benzimidazole (GB), significant activity resulted with 2-8 treatments begun 58 h after infection. The same treatment schedule using 136 mg/kg per injection of LY122771-72, 90 mg/kg per injection of LY127123, 136 mg/kg per injection of HBB and 68 mg/kg per injection of GB produced no effect. Guanidine-associated tremors were also enhanced by the addition of the substituted benzimidazoles. When guanidine was reduced to 48 mg/kg per injection, 34 mg/kg per injection of LY122771-72 was required to produce a significant reduction in the death rate and no tremors were observed.
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D003384:Coxsackievirus Infections / Q000188:drug therapy*; D004338:Drug Combinations; D004357:Drug Synergism; D004770:Enterovirus; D019791:Guanidine; D006146:Guanidines / Q000627:therapeutic use*; D051379:Mice; D010091:Oximes; D013329:Structure-Activity Relationship; D013449:Sulfonamides
D000998:Antiviral Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D006146:Guanidines; D010091:Oximes; D013449:Sulfonamides; C020359:2-hydroxybenzylbenzimidazole; C032996:2-benzimidazolylguanidine; C037074:enviradene; C021595:viroxime; D019791:Guanidine