Acute systemic toxicity and antihypertensive activity of a novel todralazine analog in rats

Acta Pol Pharm. 1993;50(4-5):327-30.

Abstract

Acute intravenous toxicity and antihypertensive activity of KB1, a novel todralazine analog was investigated and compared with the effects of todralazine (Td) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. LD50 values were 72 mg.kg-1 for KB1, and 255 mg.kg-1 for Td in WKY and 43 mg.kg-1 or KB1 in SHR. Therefore, the toxicity of KB1 was higher than that of Td and it increased in SHR. The antihypertensive activity of KB1 (ED20% 9.8 mg.kg-1) in WKY was about 9 times less potent in comparison with Td (ED20% 1.1 mg.kg-1). Blood pressure reducing activity of KB1 augmented apparently in SHR (ED20% 2.5 mg.kg-1) whereas Td had not such an effect (ED20% 1.0). Thus, the influence of Td on blood pressure was similar in normotensive and hypertensive animals. Our results indicate that KB1 is capable of reducing blood pressure preferentially in hypertension.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Hypertension / drug therapy*
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Todralazine / analogs & derivatives*
  • Todralazine / pharmacology
  • Todralazine / therapeutic use
  • Todralazine / toxicity*

Substances

  • Todralazine