title: Calcium antagonistic and spasmolytic activities of a new 1,5-benzothiazepine derivative in isolated canine and monkey arteries.
abstract: 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.
authors.affiliation: Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kikkawa
authors.forename: S
authors.initials: S
authors.lastname: Murata
authors.forename: T
authors.initials: T
authors.lastname: Nagao
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004110:Diltiazem / Q000031:analogs & derivatives*; D015237:Dinoprost; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010108:Oxyhemoglobins / Q000494:pharmacology; D010276:Parasympatholytics; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D010108:Oxyhemoglobins; D010276:Parasympatholytics; D011450:Prostaglandin Endoperoxides, Synthetic; D011460:Prostaglandins F; D013841:Thiazepines; D012701:Serotonin; C056595:clentiazem; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D004110:Diltiazem; D002118:Calcium