Influence of atropine on the acute toxicity of isometamidium

The effectiveness of atropine in blocking the acute toxic effects of the antitrypanosomal drug isometamidium (ISMM) was evaluated in mice and goats using lethality as the primary index. The median lethal dose (LD50) of ISMM in nonatropinized mice was 45.3 mg/kg bodyweight (SE +/- 5.3 mg/kg bodyweight), whereas the LD50 of ISMM in mice pre-treated with atropine was 71.7 mg/kg bodyweight (SE +/- 13.2 mg/kg bodyweight). The increase in LD50 was about 60%. The ratio of the slope of the dose-response curve for ISMM in non-atropinized mice to that in atropinized mice was about 4:1. The results showed that atropine was effective in considerably reducing the lethal effect of ISMM in mice. In contrast, experiments in goats showed markedly different results; atropine was not effective in reducing the lethality of ISMM. It was concluded that in mice atropine has some beneficial action in cases of overdosage or poisoning by ISMM. Treatment with atropine should be attempted as an antidotal measure in humans accidentally poisoned with ISMM.