A subchronic study of the toxicity of an orally administered benzoquinolizinyl derivative in the rat and dog.
The subchronic toxicity of the trans isomer of N-(1,3,4,6,7-hexahydro-11bH-benzo[a] quinolizin-2-yl) propionanilide hydrochloride (TR2379), a new antihypertensive agent, was studied in rats and dogs. TR2379 was well tolerated for 13 weeks at daily p.o. doses up to 200 mg/kg in the rat and 70 mg/kg in the dog. However, severe toxic manifestations, including death, were elicited in the rat at 820 mg/kg and in the dog at 160 mg/kg. Toxicity in both species was characterized by a reduction in body weight gain and an increase in the weight of several organs, (liver, heart, kidneys, adrenals, and thyroids). Serum alkaline phosphatase, which was not assayed in the rat, was markedly increased in the dog. Microscopic examination of the various tissues revealed no evidence of organ pathology in either species.