Jeppsson A B, Källström B L, Waldeck B
Department of Pharmacology 2, Astra Draco AB, Lund, Sweden.
Pharmacol Toxicol. 1992 Oct;71(4):272-7. doi: 10.1111/j.1600-0773.1992.tb00982.x.
The actions of and interaction between formoterol and salmeterol were studied on guinea-pig trachea in vitro. Tracheal strip preparations were contracted by 1 mumol/l carbachol giving a near maximal contraction. Salmeterol in concentrations from 0.1 to 3 mumol/l relaxed the tracheal smooth muscle by about 30 per cent of the maximum relaxation produced by theophylline. Formoterol caused a concentration-dependent and almost complete relaxation with a pD2 of 8.56. In the presence of salmeterol there was a rightward shift of the concentration-response curve for formoterol. The pA2 for salmeterol was estimated to 7.42. Similar experiments with isoprenaline indicated that salmeterol has a low affinity for beta 1-adrenoceptors. Formoterol and salmeterol both inhibited in a concentration-dependent manner the contractions evoked by stimulation of the vagus nerve in a tracheal tube preparation. The degree of inhibition decreased with increasing stimulation frequency. Complete inhibition was attained with salmeterol, but not with formoterol, at the highest frequency employed (45 Hz). The inhibiting effect of 10 mumol/l salmeterol was not blocked by 10 mumol/l sotalol, a beta-adrenoceptor antagonist. It is concluded that salmeterol, in comparison to formoterol, is a partial beta 2-adrenoceptor agonist and has, at high concentrations, an additional unspecific inhibitory action.
在体外对豚鼠气管研究了福莫特罗和沙美特罗的作用及相互作用。气管条制备物用1μmol/L卡巴胆碱收缩，产生接近最大收缩。浓度为0.1至3μmol/L的沙美特罗使气管平滑肌松弛约为茶碱产生的最大松弛的30%。福莫特罗引起浓度依赖性且几乎完全的松弛，其pD2为8.56。在存在沙美特罗的情况下，福莫特罗的浓度-反应曲线向右移动。沙美特罗的pA2估计为7.42。用异丙肾上腺素进行的类似实验表明，沙美特罗对β1肾上腺素能受体的亲和力较低。福莫特罗和沙美特罗均以浓度依赖性方式抑制气管插管制备物中迷走神经刺激引起的收缩。抑制程度随刺激频率增加而降低。在所用的最高频率（45Hz）下，沙美特罗可实现完全抑制，但福莫特罗不能。10μmol/L沙美特罗的抑制作用未被10μmol/L索他洛尔（一种β肾上腺素能受体拮抗剂）阻断。结论是，与福莫特罗相比，沙美特罗是一种部分β2肾上腺素能受体激动剂，且在高浓度时有额外的非特异性抑制作用。
