Pendleton R G, Williams M, Chung C, Cook P, Risley E
Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(3):210-4. doi: 10.1007/BF00505320.
Certain tricyclic drugs, some of which are primarily used clinically as antidepressants, have been shown to act as gastric antisecretory agents. The anatomical site(s) and mechanism(s) of action of these agents is, however, in most cases unclear. In this study, we found that desmethylimipramine (DMI) was approximately 28 times more potent in inhibiting gastric acid secretion when administered intracerebroventricularly (i.c.) than when administered intravenously (i.v.) in pylorus-ligated rats, which is indicative of a site of action in the central nervous system. Qualitatively similar results were obtained with pirenzepine where the i.c./i.v. potency ratio was 8. Doxepin also preferentially inhibited acid secretion when given i.c. at low but not at high doses. Atropine and chlorpromazine were equipotent antisecretory agents by both routes of administration. Doxepin and DMI but not pirenzepine were effective inhibitors of brain stem norepinephrine uptake in vitro thus making this an unlikely common mechanism to explain the central actions of these compounds.
某些三环类药物，其中一些在临床上主要用作抗抑郁药，已被证明可作为胃抗分泌剂。然而，在大多数情况下，这些药物的作用解剖部位和作用机制尚不清楚。在本研究中，我们发现，在幽门结扎的大鼠中，去甲丙咪嗪（DMI）经脑室注射（i.c.）时抑制胃酸分泌的效力比静脉注射（i.v.）时高约28倍，这表明其作用部位在中枢神经系统。用哌仑西平获得了定性相似的结果，其i.c./i.v.效力比为8。多塞平在低剂量而非高剂量经脑室注射时也优先抑制胃酸分泌。阿托品和氯丙嗪通过两种给药途径都是等效的抗分泌剂。多塞平和DMI而非哌仑西平在体外是脑干去甲肾上腺素摄取的有效抑制剂，因此这不太可能是解释这些化合物中枢作用的共同机制。
