[Toxicologic study on the antihypertensive agent urapidil].
The acute toxicity of 6-(3-[4-(o-methoxyphenyl)-1-piperazinyl-propylamino)-1,3-dimethyluracil (urapidil, Ebrantil) was tested in rats and mice using oral and intravenous routes. The tolerance upon repeated oral administration was tested in subacute and chronic toxicity studies lasting 3 weeks, 3, 6 and 12 months in the rat, as well as studies lasting 4 weeks and 6 months in the dog. The effect of urapidil on the reproduction in mice, rats and rabbits was also investigated. Sedation is seen in mice and rats after a single administration of urapidil, at lethal doses, tremor and convulsions appear. The same symptoms were seen in experiments with repeated oral administration in the rat (stomach tube) or in the dog (tablets) as the criterium of tolerance. In feeding  studies in the rat, the decreased body weight gain was the criterium of toxicity. The no-effect dose in the rat is 42 times the therapeutic dose in man. The no-effect dose in the dog lies between 8 and 21 times the average therapeutic dose. An inhibition of the estrus cycle in the rat proved to be species-specific. In reproductin studies, significant toxic effects were seen besides functional disturbances specific to the rat. Urapidil was not teratogenic. The development and reproductive capacity of the F1-generation was not affected.
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D013997:Time Factors; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity
D000959:Antihypertensive Agents; D014498:Uracil
Toxikologische Prüfung des Antihypertensivums Urapidil.