Pharmacological properties of YM17E, an Acyl-CoA:cholrsterol acyltransferase inhibitor, and diarrheal effect in beagle dogs
-
- Kashiwa Makoto
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Masuyama Yoichi
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Miyauchi Hiromi
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Uchida Taisuke
- Drug Metabolism Department, Yamanouchi Pharmaceutical Co., Ltd.
-
- Naganuma Shin
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Kakuta Hirotoshi
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Terada Motoko
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Kiriyama Takashi
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Matsuda Koyo
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Ito Noriki
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Iizumi Yuichi
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
-
- Takenaka Toichi
- Cardiovascular and Atherosclerosis Research Laboratories, Yamanouchi Institute for Drug Discovery Research
書誌事項
- タイトル別名
-
- Pharmacological Properties of YM17E, an Acyl-CoA:Cholesterol Acyltransferase Inhibitor, and Diarrheal Effect in Beagle Dogs.
- Pharmacological Properties of YM17E an
- Pharmacological properties of YM17E, an acyl-CoAxholesterol acyltransferase inhibitor, and diarrheal effect in beagle dogs
この論文をさがす
抄録
YM17E (1, 3-bis[[1-cycloheptyl-3-(p-dimethylaminophenyl)ureido]methyl]benzene dihydrochloride)was found to be a potent inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT)in rabbit liver and intestine microsomes. Dixon plot analysis revealed that YM17E inhibited microsomal ACAT in a non-competitive manner. YM17E induced a marked decrease in serum cholesterol, especially in non-highdensity lipoprotein (HDL)fractions, in cholesterol-fed rats and rats fed normal chow. Measurement of bile secretion after oral administration of YM17E in cholesterol-fed rats showed that the drug markedly accelerated the secretion of bile acids and neutral sterols. Furthermore, absorption of [3H]cholesterol from the gut of cholesterol-fed rats was significantly inhibited by YM17E. From these results, the hypocholesterolemic activity of YM17E in these animals resulted from both a decrease in cholesterol absorption from the gut and the stimulation of excretion of cholesterol from the liver into bile. However, YM17E caused secretory diarrhea in beagle dogs at near lipid lowering doses. When YM17E was administered at the same total dosage but divided into 5 daily administrations, the incidence of diarrhea was significantly reduced while its cholesterol lowering effect became stronger. These results suggest that the inhibition of intestinal and/or liver ACAT increases the risk of diarrhea development which, however, can be avoided by controlled drug administration in beagle dogs.
収録刊行物
-
- Jpn.J.Pharmacol.
-
Jpn.J.Pharmacol. 73 (1), 41-50, 1997
公益社団法人 日本薬理学会
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1390001204286711680
-
- NII論文ID
- 10008676832
-
- NII書誌ID
- AA00691188
-
- COI
- 1:CAS:528:DyaK2sXnsFCqtw%3D%3D
-
- ISSN
- 13473506
- 00215198
-
- NDL書誌ID
- 4131794
-
- PubMed
- 9032133
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可