Studies on A New 1, 5-Benzothiazepine Derivative (CRD-401)

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)-l, 5-benzothiazepine-4 (5H)-one hydrochloride, produced a potent coronary vasodilator effect in anesthetized dogs. Among four Ttereoisomers of the compound, d- and l-isomers of cis- and transforms, 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 increase in coronary blood flow resulted. The present report deals with the vasodilator action of d-cis-isomer of the new benzodiazepine 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-cis-isomers 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 anesthetized dogs and on the coronary vessels in isolated hearts of the guinea pig.