Acute toxicity study of KB-944, a new calcium antagonist

The acute toxicity of diethyl 4-(benzothiazol-2-yl)benzylphosphonate (KB-944) was studied in mice, rats and dogs: In mice and rats, toxic symptoms such as deceleration of spontaneous movement, ataxic gait, disappearance of righting reflex, reduction in body temperature and suppression of breathing appeared following administration of a single dose of KB-944. The symptoms developed in dogs were depression, bradycardia and labored breathing. The LD50 values determined in male and female rats were 1622 and 1555 mg/kg, respectively, for oral administration, 2216 and 2820 mg/kg for subcutaneous injection, and 762 and 479 mg/kg for intraperitoneal injection. The LD50 values determined in male and female mice were 2807 and 3856 mg/kg, respectively, for oral administration, greater than 4000 mg/kg for subcutaneous injection, and 815 and 777 mg/kg for intraperitoneal injection. As shown above, there was no evident difference in LD50 between sexes in either species of animals. Since many of the dogs given an oral dose larger than 1000 mg/kg vomited the drug, oral LD50 value could not be determined.