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  • Title: Pharmacological profile of a new beta-adrenoceptor blocker, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696).
    Author: Nakagawa Y, Sugai T, Chin WP, Shibuya T, Hashimoto K, Imai S.
    Journal: Arzneimittelforschung; 1984; 34(2):194-9. PubMed ID: 6144313.
    Abstract:
    To characterize the pharmacological profile of a new beta-adrenoceptor blocker, 4-[3-(tert-butylamino)-2-hydroxypropoxy]-N-methylisocarbostyril hydrochloride (N-696), experiments were performed in the isolated atria and trachea of the guinea pig, in the pithed rat, in the anesthetized rabbit, in anesthetized dogs and in anesthetized open-chest dogs. Antiarrhythmic action was assessed in conscious as well as in anesthetized dogs. Although N-696 was a non-selective beta-blocker 15-20 times less potent than propranolol under in vitro conditions, it was as effective a blocker as propranolol under in vivo conditions. N-696 produced a fall of the blood pressure in the pithed rat and attenuated the blood pressure rise produced by stimulation of the preganglionic sympathetic nerve. In the anesthetized rabbits, it produced a hypotensive effect associated with an increased discharge of the renal nerve. In anesthetized dogs it produced a hypotensive effect and a decrease in the myocardial blood flow. However, the decrease in the myocardial blood flow was smaller than that produced by propranolol. All these findings indicate that N-696 has a direct vasodilatory effect besides its beta-blocking action. As a beta-blocker N-696 was unique in that it produced a potent antiarrhythmic effect in two-stage coronary ligation arrhythmia.
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