Pharmacological properties of the novel highly potent diuretic 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt.
Pharmacological properties of the novel highly potent diuretic 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt.
复制标题
新型高效利尿剂7-氯-2,3-二氢-1-(2-甲基苯甲酰基)-4(1H)-喹啉酮4-肟-O-磺酸钾盐的药理学特性。
DOI：
10.1002/chin.199313303
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Y. Orita
中科院分区：
文献类型：
--
作者：
T. Shinkawa;F. Yamasaki;A. Kikuchi;M. Nakakuki;K. Nishijima;A. Uemura;M. Mizota;Y. Orita
7-氯-2，3-二氢-1-（2-甲基苯甲酰基）-4（1H）-喹啉酮4-肟-O-磺酸钾盐（M17055，CAS 114417-20-8）在大鼠（p.o.）中显示出剂量依赖性的强效利尿和促尿盐排泄作用，小鼠（p.o.）和狗（i. v.），剂量分别为0.1-100 mg/kg、0.3-100 mg/kg和0.01-30 mg/kg。M17055的利尿、利钠和利尿氯的疗效远高于氢氯噻嗪，与呋塞米几乎相同。这些结果表明，该化合物可被归类为“高上限利尿剂”。M17055对大鼠尿钠排泄的效力（p.o.），小鼠（p.o.）和犬（i. v.）以ED_（50）值计算，分别为速尿的38、34和24倍。M17055或呋塞米给药后，钠、氯和钾的尿排泄量与尿量平行增加，而M17055单独给药时观察到尿钙和钠排泄量明显分离。在大鼠中，在类似的尿钠排泄条件下，M17055的尿钙排泄增加显著低于呋塞米。此外，在小鼠中，M17055以低有效性剂量降低尿钙排泄。在使用麻醉犬的清除率研究中，M17055在生理盐水负荷条件下抑制负游离水清除率（CH 2 O），并在水利尿条件下降低正CH 2 O。M17055诱导的CH 2 O效应的这些变化与袢利尿剂相似。然而，M17055不能将阴性CH 2 O转变为阳性，而呋塞米能够做到这一点。此外，使用M17055时，CH 2 O阳性降至几乎为零，而即使在30 mg/kg剂量下，尿液仍被呋塞米稀释。（250字处删节）
7-Chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid potassium salt (M17055, CAS 114417-20-8) showed potent diuretic and saluretic effects dose-dependently, in rats (p.o.), mice (p.o.) and dogs (i.v.), at doses of 0.1-100 mg/kg, 0.3-100 mg/kg and 0.01-30 mg/kg, respectively. The efficacy of M17055 for diuresis, natriuresis and chloruresis was much higher than that of hydrochlorothiazide and almost the same as that of furosemide. These results indicate that this compound may be classified as a "high ceiling diuretic". The potencies of M17055 for natriuresis in rats (p.o.), mice (p.o.) and dogs (i.v.) calculated with ED50 values were 38, 34 and 24 times, respectively, more potent than those of furosemide. Urinary excretions of sodium, chloride and potassium increased in parallel with urinary volume with the administration of M17055 or furosemide, whereas an apparent dissociation with urinary calcium and sodium excretion was observed with M17055 alone. In rats, the increase of urinary calcium excretion with M17055 was significantly lower than that with furosemide under comparable conditions of natriuresis. Moreover, in mice, M17055 decreased urinary calcium excretion at doses with low effectiveness. In clearance studies using anesthetized dogs, M17055 suppressed negative free water clearance (CH2O) under saline loaded conditions, and it decreased positive CH2O under water diuretic conditions. These changes in the effects on CH2O induced by M17055 resemble those of loop diuretics. However, M17055 could not shift negative CH2O to positive, while furosemide was able to do so. Moreover, positive CH2O decreased to nearly zero with M17055, while urine remained dilute with furosemide even at 30 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)