Anti-spasmogenic and spasmolytic effects of BRL 34915: a comparison with nifedipine and nicorandil.
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 rather than receptor-operated Ca2+ channels.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010276:Parasympatholytics; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits
D001578:Benzopyrans; D010276:Parasympatholytics; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D011189:Potassium Chloride; D009543:Nifedipine; D009638:Norepinephrine