Pendleton R G, McCafferty J P, Roesler J M, Hieble J P
Eur J Pharmacol. 1981 Nov 5;75(4):171-8. doi: 10.1016/0014-2999(81)90542-2.
The mechanism for the gastric antisecretory action of desmethylimipramine (DMI) was studied using the pylorus-ligated rat preparation. DMI was approximately 40 times more potent in decreasing gastric acid secretion when given into the lateral ventricles of the brain than when administered intravenously. The antisecretory effects of DMI could be blocked by the alpha 2-adrenoceptor antagonists yohimbine and SK&F 72223 and mimicked by central administration of an alpha 2-agonist. It could not be blocked by the alpha 1-antagonist prazosin or mimicked by alpha 1-adrenoceptor agonists. SK&F 72223 and yohimbine themselves produced small increases in gastric acid, but the increase output by SK&F 72223 failed to reduce the antisecretory response to atropine. Since DMI is not an alpha 2-adrenoceptor agonist, but is a potent inhibitor of norepinephrine uptake, these data suggest that the effects of DMI on gastric acid secretion are mediated indirectly via inhibition of catecholamine uptake at central synapses containing alpha 2-adrenoceptors.
采用幽门结扎大鼠制备模型研究了去甲丙咪嗪（DMI）的胃抗分泌作用机制。当将DMI注入脑侧脑室时，其降低胃酸分泌的效力比静脉给药时高约40倍。DMI的抗分泌作用可被α2-肾上腺素能受体拮抗剂育亨宾和SK&F 72223阻断，并可被中枢给予α2-激动剂模拟。它不能被α1-拮抗剂哌唑嗪阻断，也不能被α1-肾上腺素能受体激动剂模拟。SK&F 72223和育亨宾本身可使胃酸略有增加，但SK&F 72223增加的胃酸分泌量未能降低对阿托品的抗分泌反应。由于DMI不是α2-肾上腺素能受体激动剂，而是去甲肾上腺素摄取的强效抑制剂，这些数据表明DMI对胃酸分泌的作用是通过抑制含α2-肾上腺素能受体的中枢突触处的儿茶酚胺摄取间接介导的。
