Acute systemic toxicity and antihypertensive activity of a novel todralazine analog in rats.
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.
Department of Pharmacology, Drug Institute, Warsaw, Poland.
Z
Z
Jastrzebski
H
H
Czyzewska-Szafran
B
B
Goźlińska
M
M
Wutkiewicz
A
A
Jedrych
Z
Z
Fijałek
K
K
Biniecki
P
P
Aranjo
L
L
Ciszewski
A P
AP
Mazurek
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014032:Todralazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*
D014032:Todralazine