作者
JC Clapham, C Wilson
发表日期
1987/9/1
期刊
Journal of Autonomic Pharmacology
卷号
7
期号
3
页码范围
233-242
简介
1 BRL 34915, nifedipine and nicorandil were compared for anti-spasmogenic activity against field stimulation (frequency-response curves), noradrenaline and KCl (concentration-response curves), and for spasmolytic activity against tissues pre-contacted with 3 X 10 (-2) and 9 X 10 (-2) M KCl, in rabbit isolated mesenteric artery. 2 BRL 34915 was an effective anti-spasmogenic agent (threshold concentration 10 (-8) M) against endogenous noradrenaline released by field stimulation, and slightly less effective (threshold concentration 10 (-7) M) against exogenous noradrenaline. Anti-spasmogenic activity of BRL 34915 against KCl was limited. BRL 34915 demonstrated spasmolytic activity against contractions to KCl 3 X 10 (-2) M (IC50= 3.7 X 10 (-7) M) but not KCl 9 X 10 (-2) M. 3 Nicorandil demonstrated anti-spasmogenic activity against all three contractile stimuli although relatively high concentrations (10 (-6)-10 (-4) M) of the drug were required. Spasmolytic activity was greater against 3 X 10 (-2) M KCl contractions (IC50= 1.0 X 10 (-5) M) than against 9 X 10 (-2) M KCl contractions (maximum relaxation of 18% at 10 (-4) M). 4 Nifedipine (10 (-9)-10 (-7) M) was a potent inhibitor of contractions over the entire KCl concentration range (1 X 10 (-2)-9 X 10 (-2) M). Nifedipine was, however, much less effective against contractions to exogenous or endogenous noradrenaline. 5 The results are consistent with the hypotheses that (a) the inhibitory activity of BRL 34915 may involve K+ channel activation,(b) the inhibition by nicorandil involves an additional mechanism (s) and (c) nifedipine is a Ca2+ channel blocker with selectivity for voltage-operated …
引用总数
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