Protective Effect of TA-993, a Novel Therapeutic Agent for Peripheral Circulatory Insufficiency, on Skeletal Muscle Fatigue in a Rat Model of Hindlimb Ischemia.
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- Doi Hisayoshi
- Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,2-2-50,Kawagishi,Toda,Saitama 335-8505,Japan
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- Kaburaki Minako
- Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,2-2-50,Kawagishi,Toda,Saitama 335-8505,Japan
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- Inoue Hirotaka
- Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,2-2-50,Kawagishi,Toda,Saitama 335-8505,Japan
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- Suzumura Kuniharu
- Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,2-2-50,Kawagishi,Toda,Saitama 335-8505,Japan
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- Narita Hiroshi
- Discovery Research Laboratory,Tanabe Seiyaku Co.,Ltd.,2-2-50,Kawagishi,Toda,Saitama 335-8505,Japan
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Abstract
TA−993(cis−(−)−2−(4−methylphenyl)−3−acetoxy−2, 3−dihydro−5−(2−dimethylaminoethyl)−8−methyl−1, 5−benzothiazepine−4(5H)−one maleate), a new 1, 5−benzothiazepine derivative, has a selective increasing action on limb blood flow in addition to an antiplatelet action.In this report we studied the effect of TA−993 on a time dependent decrease in developed tension of electrically−induced contraction of tibialis anterior muscle in a rat model of peripheral circulatory insufficiency induced by occlusion of abdominal aorta.In our preparation, the developed tension decreased by 20−30% in a sham−operated group and 30−40% in an abdominal aorta−occluded group at the end of the experimental period of 60 min.Intraduodenal administration(i.d.)of TA−993(10 mg/kg)to the abdominal aorta−occluded rats ameliorated the decrease in developed tension to the level of the sham−operated group.Moreover, TA−993 at 10 mg/kg, i.d.significantly increased femoral arterial blood flow supplied through collateral circulation and decreased the whole blood viscosity in this model.These results suggest that TA−993 improves dysfunction of skeletal muscle contraction due to peripheral circulating insufficiency through an increase in collateral blood flow and an improvement of red blood cell deformability.
Journal
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- The Japanese Journal of Pharmacology
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The Japanese Journal of Pharmacology 83 (1), 73-81, 2000
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390001204286879616
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- NII Article ID
- 10008184451
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- NII Book ID
- AA00691188
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- COI
- 1:CAS:528:DC%2BD3cXjs12ju7k%3D
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- ISSN
- 13473506
- 00215198
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- NDL BIB ID
- 5399726
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- PubMed
- 10887943
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed