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.
Jastrzebski
Z
Z
Department of Pharmacology, Drug Institute, Warsaw, Poland.
Czyzewska-Szafran
H
H
Goźlińska
B
B
Wutkiewicz
M
M
Jedrych
A
A
Fijałek
Z
Z
Biniecki
K
K
Aranjo
P
P
Ciszewski
L
L
Mazurek
A P
AP
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