Studies on a New 1, 5-Benzothiazepine Derivative (Crd-401) Iii. Effects of Optical Isomers of CRD-401 on Smooth Muscle and Other Pharmacological Properties

Nagao, Taku; Sato, Masanori; Iwasawa, Yoshio; Takada, Toshikazu; Ishida, Ryuichi; Nakajima, Hiromichi; Kiyomoto, Akio

doi:10.1254/jjp.22.467

Cited by 79 publications

(22 citation statements)

References 2 publications

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“…It also increased coronary blood flow when myocardial oxygen consumption diminished. Furthermore, as will be shown in the succeeding report (11), the d-, dl and l-cis-isomers of the benzothiazepine derivative produced a relaxing effect on the isolated smooth muscle in a manner similar to papaverine. All these facts support the above assumption about the property of the test compound.…”

Section: ) Effect Of Diphenhydraminesupporting

confidence: 53%

Studies on a New 1, 5-Benzothiazepine Derivative (Crd-401)

et al. 1972

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In a previous report (1), it was shown that a new 1, 5-benzothiazepine derivative, 3-acetoxy-2, 3-dihydro-5-[2-(diethylamino) ethyl]-2-(p-methoxyphenyl)-1, 5-benzothiazepine-4 (5H)-one hydrochloride, produced a potent coronary vasodilator effect in anesthetized dogs. Among four stereoisomers of the compound, d-and l-isomers of cis-and trans forms, the d-cis-isomer (CRD-401) exhibited the most powerful effect when injected into the femoral vein. Without increase in myocardial oxygen consumption, a significant in crease in coronary blood flow resulted.
The present report deals with the vasodilator action of d-cis-isomer of the new ben zothiazepine derivative under the influence of various pharmacological blockers. The results are considered in relation to the mechanism of the compound. Effects of dl-and l-cisisomers and dl-trans-isomer were also investigated and compared with the action of d-cis-isomer. Experiments were performed on the coronary and femoral arteries in anes thetized dogs and on the coronary vessels in isolated hearts of the guinea pig. MATERIALSAND METHODS Coronary artery blood flowMale dogs weighing 15-25 kg were anesthetized using sodium pentobarbital (30 mg/ kg, i.v.) and the chest was opened by the removal of a portion of the left fourth rib under positive pressure respiration (room air). According to the method of Eckenhoff et al. (2), the blood from the left carotid artery was led to the anterior descending coronary artery by a short extracorporeal loop. The blood fow was then measured by means of an electro magnetic flowmeter (Nihon Koden, MF-2), which was introduced into the loop. Femoral arterial pressure was obtained and recorded via a pressure transducer as well as the coronary blood flow into a multipurpose polygraph (Nihon Koden, RM-150). Femoral artery blood flowMale dogs (10-14 kg) were anesthetized using sodium pentobarbital (30 mg/kg, i.v.).A short extracorporeal loop was introduced into the left femoral artery and the blood flow was measured by the same procedure described above. The test compound, in a volume not exceeding 0.5 ml, was injected into the extracorpo

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Section: ) Effect Of Diphenhydraminesupporting
confidence: 53%

Studies on a New 1, 5-Benzothiazepine Derivative (Crd-401)
NAGAO
¹
,
Sato
²
,
Nakajima
³

et al. 1972
Jpn.J.Pharmacol
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79
2
18
0
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“…This discrepancy might due to the difference between tissues or experimental conditions used. Nagao et al (27) reported that diltiazem had a local anesthetic activity with an ED50 value of 0.28%, that is 6.2 x10-3 M. However, it is unlikely that the inhibition of the TNS-evoked tritium overflow by diltiazem is caused by its local anesthetic activity since the concentrations of diltiazem used in the present study are lower than those required for local anesthetic activity, judging from the result of Nagao et al (27). Langer and Shepperson (25) reported that diltiazem in concentrations up to 10-4 M had no significant effect on the contractile response of superfused canine saphenous vein to norepinephrine.…”

Section: Nicardipinementioning
confidence: 99%

Effects of Ca Antagonists on the Norepinephrine Release and Contractile Responses of Isolated Canine Saphenous Veins to High KCl
Takata
¹
,
Kato
²

1985
Japanese Journal of Pharmacology
24
7
23
1
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“…On the other hand, in isolated vascular smooth muscle of dog coronary artery or rabbit aorta, diltiazern antagonizes calcium ion and thus causes a relaxing effect (5). It was also demonstrated that the compound sup presses the contraction of isolated guinea pig taenia coli in both normal and K+-rich solutions (7,8). The membrane effect of diltiazem on the smooth muscle, however, remained un examined.…”

mentioning
confidence: 99%

Effects of Diltiazem on Electrical and Mechanical Activities of Isolated Guinea Pig Taenia Coli
Magaribuchi
¹
,
Nakajima
²
,
Kiyomoto
³

1977
Japanese Journal of Pharmacology
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30
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7
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Abstract--Effects of diltiazem on electrical and mechanical activities of isolated guinea pig taenia coli were studied by means of the double sucrose-gap method.In the spon taneously active preparations, diltiazem (2.2 x l0-1 M) suppressed both electrical activity and isometric contraction, while electrical and mechanical activities evoked by the depolarizing current pulse were not affected at the concentration of 2.2 x 10-1 M. In the presence of 2.2 10_; M diltiazem, the evoked contractile force and the number of repetitive firings during depolarization were reduced, whereas the single spike was almost unchanged or somewhat inhibited. At 2.2 >' 10-4 M diltiazem, both electrical and mechanical activities were almost abolished. The contractile force and single spike suppressed by diltiazem were partly reversed by the addition of 5 mM CaCI,.

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Studies on a New 1, 5-Benzothiazepine Derivative (Crd-401) Iii. Effects of Optical Isomers of CRD-401 on Smooth Muscle and Other Pharmacological Properties

Cited by 79 publications

References 2 publications

Studies on a New 1, 5-Benzothiazepine Derivative (Crd-401)

Studies on a New 1, 5-Benzothiazepine Derivative (Crd-401)

Effects of Ca Antagonists on the Norepinephrine Release and Contractile Responses of Isolated Canine Saphenous Veins to High KCl

Effects of Diltiazem on Electrical and Mechanical Activities of Isolated Guinea Pig Taenia Coli

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