Eltze M, Gönne S, Riedel R, Schlotke B, Schudt C, Simon W A
Eur J Pharmacol. 1985 Jun 7;112(2):211-24. doi: 10.1016/0014-2999(85)90498-4.
The new antisecretory drug, telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno-[3,4 - b][1,5]benzodiazepin-10-one), was investigated for its inhibition of functionally intact muscarinic receptors involved in gastric acid secretion in rabbit fundic glands, perfused mouse stomach in vitro, perfused rat stomach in situ, gastric fistula in rats and dogs with a Heidenhain pouch. The effects on these receptors were contrasted with effects on receptors located on smooth muscle and heart, i.e. isolated rat urinary bladder, stomach and atrium. The results were compared to those values obtained with nonselective antimuscarinic drugs (N-methylscopolamine, atropine) and the selective M-1 antagonist pirenzepine. Telenzepine was found to be 4-10 times more potent than pirenzepine with respect to depressing both gastric acid secretion and smooth muscle or myocardial responses. Based on -log EC50 and pA2 values, both drugs exhibited a similar selectivity profile differing from the pattern of effects observed with atropine or a second reference compound, zolenzepine. As compared with atropine, telenzepine exhibited a 5 fold higher relative affinity to muscarinic receptors involved in gastric acid secretion. It was concluded that telenzepine is selective to discriminate between muscarinic receptors mediating gastric acid secretion and affecting muscle contractility and that this finding supports the concept of muscarinic receptor heterogeneity.
新型抗分泌药物替仑西平（4,9 - 二氢 - 3 - 甲基 - 4 - [(4 - 甲基 - 1 - 哌嗪基)乙酰基] - 10H - 噻吩并[3,4 - b][1,5]苯二氮䓬 - 10 - 酮），在兔胃底腺、体外灌注的小鼠胃、原位灌注的大鼠胃、大鼠和犬的胃瘘（海登海因小胃）中，对参与胃酸分泌的功能完整的毒蕈碱受体的抑制作用进行了研究。将其对这些受体的作用与对位于平滑肌和心脏上的受体（即离体大鼠膀胱、胃和心房）的作用进行了对比。结果与用非选择性抗毒蕈碱药物（N - 甲基东莨菪碱、阿托品）和选择性M - 1拮抗剂哌仑西平所获得的值进行了比较。发现替仑西平在抑制胃酸分泌和平滑肌或心肌反应方面比哌仑西平强4 - 10倍。根据 - log EC50和pA2值，两种药物表现出相似的选择性特征，不同于用阿托品或第二种参比化合物佐仑西平观察到的效应模式。与阿托品相比，替仑西平对参与胃酸分泌的毒蕈碱受体的相对亲和力高5倍。得出的结论是，替仑西平对于介导胃酸分泌的毒蕈碱受体与影响肌肉收缩力的毒蕈碱受体具有选择性区分作用，这一发现支持了毒蕈碱受体异质性的概念。
