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  • Title: Actions of nipradilol (K-351), a new alpha- and beta-adrenoceptor blocker, on the rabbit portal vein.
    Author: Nanjo T, Kitamura K.
    Journal: Jpn J Pharmacol; 1984 Aug; 35(4):359-69. PubMed ID: 6150128.
    Abstract:
    Nipradilol but not desnitro nipradilol [N-) nipradilol) inhibited the norepinephrine (NE)-induced depolarization and contraction of the rabbit portal vein. The NE-induced contraction and depolarization were also blocked by prazosin, but not blocked by yohimbine. Therefore, nipradilol possesses an alpha 1-blocking action. The order of potency was prazosin greater than nipradilol greater than yohimbine greater than (N-)-nipradilol = 0. With applications of field stimulations to muscle tissues, the smooth muscle membrane was depolarized with a latency of several seconds, and the action potential was generated. These phenomena were blocked by tetrodotoxin (TTX), prazosin or nipradilol, but not by yohimbine. Isoproterenol (Isop) inhibited the 30 mM K-induced contraction, and this inhibitory action was blocked by (N-), nipradilol, nipradilol or propranolol, dose-dependently. The potency of beta-blocking actions of nipradilol was much the same as that observed by propranolol and (N-) nipradilol. When nipradilol (10(-5) M) was applied to the tissue, the amplitude of the 30 mM K contraction was slightly reduced. Such inhibitory action was not observed by application of (N-) nipradilol. The Ki values of nipradilol for blocking actions on the NE-induced contraction and Isop-induced relaxation were of the same order of 10(-7) M. Therefore, the potencies of alpha 1-blocking and beta-blocking actions of nipradilol may be the same in the rabbit portal vein. These findings suggest that the vasodilating action of nipradilol on the rabbit portal vein is mainly due to the alpha 1-blocking action and that the nitrate action of this agent may be weak.
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