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.