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KMID : 0606920060140040253
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Biomolecules & Therapeutics
2006 Volume.14 No. 4 p.253 ~ p.258
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Acute Toxicity of the BKCa Channel Opener LDD175
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Choi Ji-Young
Choi Jong-Hyun
Lee Geum-Seon
Ko Hong-Sook
Park Chul-Seung
Kim Yong-Chul
Cheong Jae-Hoon
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Abstract
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LDD175 (4-choloro-7-trifluoromethyl-10H-benzo [4,5]furo[3,2-b]indole-1-carboxylic acid) is one of benzofuroindole derivatives that act as a potent BKCa channel openers. In the process of testing LDD175 as a new drug candidate, an acute toxicity study was carried out in mice. The mice were administered LDD175 intraperi- toneally at dose of 0.2, 1, 10, 50, 100, 200, 400, 800 mg/kg and orally at dose of 10, 100, 400, 800 mg/kg body weight. After administering LDD175, the vital organs such as the liver, kidney and spleen were carefully obscrved for any significant pathological fcatures or differences from the norm over a 14-day period. LDD175 did not induce any short-term toxicity at dosed less than 100 mgl/kg. A LD50 of LDD175 was 2493 mg/kg inmale mice and 4908 mg/kg in female mice. Weight reduction was observed at a dose of 800 mg/kg in male, and 400 and 800 mg/kg im female. The kidney weight decre sed in female after an intraperitoneal injection of LDD 175 high dose (＞ 400 mg/kg, i.p.), and the spleen weight increased in the male (800 mg/kg, i.p.) and female (400mg/kg, i.p) mice. Inspite of the change in organ weights, there were neither histopathological changes nor any gross mor- phological abnormalities detected in any organ. LDD 175 did not produce significant changes in the general behavior at dosed of ＜ 200 mg/kg, but decreased locomotor activity was observed at an intraperitoneal dose of 400 mg/kg. Its effects on the locomotor activity and activity on the rotarod were tested and compared with the effects of diazepam 5 mg/kg. The decrement in the locomotor activity and the activity on the rotarod induced by LDD 175 was less serious than in by diazepam.
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KEYWORD
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LDD175, acute toxicity, locomotor activity, BKCa channel opener
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