First Department of Medicine, Medical and Health Centre, University of Pecs, H-7624, Hungary.
Curr Pharm Des. 2013;19(1):84-9. doi: 10.2174/13816128130112.
Actions of various drugs have been tested on the gastric acid basal secretion and on the drug (Indomethacin)- induced gastric mucosal damage; however their physiological and pharmacological mechanisms have not been compared.
The effects of capsaicinoids, atropine, cimetidine, omeprazole, famotidine and ranitidine were studied on gastric basal acid output, whereas the gastric mucosal preventive effects of capsaicinoids (capsaicin), atropine and cimetidine were tested on the indomethacin-induced gastric mucosal microbleedings in human healthy subjects. Results were presented by molecular pharmacological method; affinity (pD) and intrinsic activity (α-values) were calculated. Intrinsic activity curves are based on comparison to atropine effect (α(atropine)= 1.00). For evaluation of physiological and pharmacological effects of compounds molar doses of pD(2) (necessary doses to produce 50% inhibition) and pA(2) (50% inhibion on intrinsic activity) were calculated from affinity and intrinsic activity curves.
The pD(2) values for compounds were as follows: 5.88 for capsaicinoids, 5.40 for atropine , 2.23 for cimetidine, 3.33 for ranitidine, 3.77 for famotidine and 3.97 for omeprazole. α - value results for compounds were: 0.76 for capsaicinoids, and 1.00 for atropine, cimetidine, ranitidine, famotidine and omeprazole all equal to 1.00 on gastric acid basal secretion. The pD(2) values on indomethacin-induced gastric mucosal microbleeding were found as follows: 6.00 for capsaicinoids, 5.50 for atropine, and 3.50 for cimetidine, meanwhile α-values resulted 0.76 for capsaicinoids, 1.00 for atropine and cimetidine.
Comparison classical antisecretory drugs acting on different pathways but in much more higher molar concentrations. The atropine and capsaicinoids act in about the same molar concentration which suggests a significant physiological role for capsaicin sensitive afferent nerves in the regulation of gastric basal acid secretion and in the prevention of chemically- induced gastric mucosal protection in human healthy subjects, suggesting a novel physiological pathway in regulation. These results clearly indicate the molecular pharmacological backgrounds of actions of classical antisecretory drugs and physiological role of capsaicin- sensitive afferent nerves in human healty subjects on the gastric basal secretion and on the prevention of drug-induced gastric mucosal damage.
已经测试了各种药物对胃酸基础分泌和药物（吲哚美辛）诱导的胃黏膜损伤的作用；然而，它们的生理和药理学机制尚未得到比较。
研究辣椒素类、阿托品、西咪替丁、奥美拉唑、法莫替丁和雷尼替丁对胃基础酸分泌的影响，同时研究辣椒素类（辣椒素）、阿托品和西咪替丁对健康人体吲哚美辛诱导的胃黏膜微出血的胃黏膜预防作用。结果采用分子药理学方法表示；亲和力（pD）和内在活性（α 值）计算。内在活性曲线基于与阿托品作用的比较（α（阿托品）= 1.00）。为了评估化合物的生理和药理作用，从亲和力和内在活性曲线计算摩尔剂量 pD（2）（产生 50%抑制所需的剂量）和 pA（2）（对内在活性的 50%抑制）。
化合物的 pD（2）值如下：辣椒素类为 5.88，阿托品为 5.40，西咪替丁为 2.23，雷尼替丁为 3.33，法莫替丁为 3.77，奥美拉唑为 3.97。化合物的 α 值结果为：辣椒素类为 0.76，阿托品、西咪替丁、雷尼替丁、法莫替丁和奥美拉唑均为 1.00，均等于胃酸基础分泌的 1.00。在吲哚美辛诱导的胃黏膜微出血中发现的 pD（2）值如下：辣椒素类为 6.00，阿托品为 5.50，西咪替丁为 3.50，同时 α 值为 0.76，阿托品和西咪替丁为 1.00。
与作用于不同途径但在更高摩尔浓度下的经典抗分泌药物进行比较。阿托品和辣椒素类以相似的摩尔浓度起作用，这表明在人类健康受试者的胃酸基础分泌和化学诱导的胃黏膜保护中，辣椒素敏感传入神经具有重要的生理作用，提示存在新的调节生理途径。这些结果清楚地表明了经典抗分泌药物的分子药理学背景以及在人类健康受试者的胃酸基础分泌和药物诱导的胃黏膜损伤预防中，辣椒素敏感传入神经的生理作用。
