FIELDEN R, ROE A M, WILLEY G L
Br J Pharmacol Chemother. 1964 Dec;23(3):486-507. doi: 10.1111/j.1476-5381.1964.tb01605.x.
Ethyldimethyl(7-methylcoumaran-3-yl)ammonium iodide (SK&F 90,109) and its guanidine analogue [N-(7-methylcoumaran-3-yl)guanidine nitrate] (SK&F 90,238) abolish the effects of adrenergic nerve stimulation in cats, as do xylocholine and bretylium. SK&F 90,109 has slight sympathomimetic actions; these are less marked than in SK&F 90,238. Large doses of SK&F 90,109 have an action, dependent on local noradrenaline stores, that delays the appearance of adrenergic-neurone blockade in conscious cats. Responses to adrenaline are, in general, enhanced by each drug, but SK&F 90,238 transiently antagonizes tachycardia induced by adrenaline and isoprenaline. Both drugs inhibit the release of noradrenaline from the spleen during splenic nerve stimulation, but the release of catechol amines from the adrenal glands, in response to electrical or chemical stimulation, is unimpaired. In contrast to the prolonged adrenergic-neurone blocking action, any inhibition of the effects of cholinergic nerve stimulation is transient. Large intravenous doses produce neuromuscular blockade. The compounds have a slight central depressant action. In contrast to reserpine and guanethidine the noradrenaline content of rat hearts is not appreciably lowered 24 hr after a single dose of either drug. Unlike xylocholine they are not local anaesthetics. Related compounds also block the effects of adrenergic-nerve stimulation. The possible modes of action of these drugs are discussed.
乙基二甲基（7-甲基香豆素-3-基）碘化铵（SK&F 90,109）及其胍类似物[N-（7-甲基香豆素-3-基）硝酸胍]（SK&F 90,238）能消除猫体内肾上腺素能神经刺激的作用，六甲铵和溴苄铵也有此作用。SK&F 90,109有轻微的拟交感神经作用；这些作用比SK&F 90,238中的作用不那么明显。大剂量的SK&F 90,109有一种作用，依赖于局部去甲肾上腺素储备，可延迟清醒猫体内肾上腺素能神经元阻滞的出现。一般来说，每种药物都会增强对肾上腺素的反应，但SK&F 90,238能短暂拮抗肾上腺素和异丙肾上腺素引起的心动过速。两种药物都能抑制脾神经刺激期间脾脏去甲肾上腺素的释放，但对肾上腺髓质因电刺激或化学刺激而释放儿茶酚胺没有影响。与延长的肾上腺素能神经元阻滞作用相反，对胆碱能神经刺激作用的任何抑制都是短暂的。大剂量静脉注射会产生神经肌肉阻滞。这些化合物有轻微的中枢抑制作用。与利血平和胍乙啶不同，单次给药后24小时，大鼠心脏的去甲肾上腺素含量没有明显降低。与六甲铵不同，它们不是局部麻醉剂。相关化合物也能阻断肾上腺素能神经刺激的作用。讨论了这些药物可能的作用方式。
