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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Calcium antagonistic and spasmolytic activities of a new 1,5-benzothiazepine derivative in isolated canine and monkey arteries.

Effects of TA-3090 ((+) (2S,3S)-3-acetoxy-8-chloro-5-(2-(dimethylamino)ethyl)-2, 3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4-(5H)-one maleate)and diltiazem on contractions induced by different spasmogens were investigated in isolated canine and monkey arteries. Ca2+-antagonistic action in canine arteries, assessed by suppression of Ca2+-induced contraction in Ca2+-free, K+-depolarizing solution, was as follows; basilar (pA2 = 8.34) greater than coronary (pA2 = 7.95) greater than renal (pA2 = 7.46) = mesenteric artery (pA2 = 7.36). The potency of TA-3090 was 10 times greater in basilar artery and 2 to 3 times greater in the other arteries than that of diltiazem. The effect of TA-3090 on the arterial segment was more persistent than that of diltiazem. Relative vasorelaxing potency of TA-3090 to diltiazem in K+-induced contractions was greatest in the basilar artery among the tested arteries of both monkeys and dogs. Spasmolytic activities of TA-3090 on 5-HT-, PGF2 alpha-, U-46619 (thromboxane A2/prostaglandin H2 agonist) and oxyhemoglobin-induced contractions in canine basilar arteries were more potent than those of diltiazem, especially on 5-HT-induced contraction. In addition, TA-3090 suppressed 3,4-diaminopyridine-induced rhythmic contraction in the canine coronary artery. These results indicate that TA-3090 has potent Ca2+-antagonistic and spasmolytic activities, and these actions are most selective for basilar artery.[1]

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