Chiba M, Miyake N, Tamada T, Fujimoto Y, Okabe S
Nihon Yakurigaku Zasshi. 1976 Nov;72(8):969-78.
CD-3400 developed by Nippon Chemiphar Co. Ltd., is a new antihypertensive agent belonging to the class of rauwolfa alkaloids. Influence of the agent on gastric mucosa, healing process of acetic acid-induced gastric ulcer and gastric juice in rats was investigated and compared with effects of reserpine and rescinnamine. CD-3400-induced gastric lesions were fewer in number than those produced with reserpine and rescinnamine in fasted rats. After a three day treatment of CD-3400 to fed rats, however, there were few gastric lesions, while reserpine- and rescinnamine-induced gastric lesions were aggravated to a greater extent that when a single administration was given to fasted rats. Influence of CD-3400, reserpine and rescinnamine on the healing process of acetic acid-induced ulcer was insignificant, but treatment with high doses of reserpine and rescinnamine resulted in death. Pretreatment with CD-3400 and reserpine produced a decrease in gastric acid and K+, and an increase in Na+. Repeated administration of reserpine for 5 days resulted in a decrease of both gastric volume and acid, while such was not seen with CD-3400. Treatment with anticholinergic agents such as atropine sulfate and atropine methylbromide inhibited CD-3400- and reserpine-induced gastric lesions. From these results, it would appear that cholinergic factors play a role in the pathogenesis of CD-3400-induced gastric lesions, as in the case with reserpine, and that the responses of these lesions to reserpine and CD-3400 correlate with changes of ionic fluxes in gastric juice.
日本化学制药株式会社研发的CD - 3400是一种新的降压药,属于萝芙木生物碱类。研究了该药物对大鼠胃黏膜、醋酸诱导的胃溃疡愈合过程及胃液的影响,并与利血平和蛇根亭宁的作用进行了比较。在禁食大鼠中,CD - 3400引起的胃部损伤数量比利血平和蛇根亭宁产生的损伤数量少。然而,在给喂食大鼠连续三天服用CD - 3400后,胃部损伤很少,而利血平和蛇根亭宁诱导的胃部损伤比给禁食大鼠单次给药时加重得更明显。CD - 3400、利血平和蛇根亭宁对醋酸诱导溃疡愈合过程的影响不显著,但高剂量的利血平和蛇根亭宁治疗导致死亡。用CD - 3400和利血平预处理会使胃酸和钾离子减少,钠离子增加。连续5天重复给予利血平会导致胃容积和胃酸都减少,而CD - 3400则未出现这种情况。用抗胆碱能药物如硫酸阿托品和甲基溴化阿托品治疗可抑制CD - 3400和利血平诱导的胃部损伤。从这些结果来看,胆碱能因素在CD - 3400诱导的胃部损伤发病机制中起作用,如同在利血平的情况一样,并且这些损伤对利血平和CD - 3400的反应与胃液中离子通量的变化相关。