Short-term toxicological studies with impromidine (SK&F 92676): a specific histamine H2-receptor agonist

Impromidine is a specific, potent histamine H2-receptor agonist. The present paper describes the results of acute and short-term repeated-dose toxicity studies with impromidine in rodents and dogs. The intravenous LD50 was 9.6 mg kg-1 in male mice, 12.7 mg kg-1 in female mice and 25.5 mg kg-1 in rats. The minimum lethal dose in dogs after 30 min intravenous infusion was 27.7 mg kg-1 during the infusion and 4 mg kg-1 within 14 days. In 12- or 14-day tests in rats by the intravenous (maximum dose 3.24 mg per kg per day) and subcutaneous (maximum dose 20 mg per kg per day) routes, impromidine had no serious toxicological effects. In 12- or 14-day studies in dogs by the i.v. (maximum dose 0.259 mg per kg per day) and intramuscular (maximum dose 0.5 mg per kg per day) routes, impromidine caused vasodilation, tachycardia and vomiting. In a few dogs, at the highest dose levels, there was erosion and irritation of the gastrointestinal tract and myocardial damage. Other minor pathological changes were seen in the liver, kidneys and pancreas. No changes were seen other than those to be expected from the pharmacological actions of impromidine as an H2-receptor agonist. Studies in anaesthetized rats, either spontaneously respiring or sustained by artificial respiration, indicate that, at acute doses, impromidine causes death by respiratory failure.