Preiss D U, Code C F
J Pharmacol Exp Ther. 1975 May;193(2):614-20.
This study was done to determine the comparative effectiveness of burimamide and metiamide as antagonists of gastric secretion stimulated by histamine and its methyl derivatives, Nalpha-methylhistamine, N-alpha,N-alpha-dimethylhistamine and 4-methylhistamine, in dogs with vagally denervated (Heidenhain pouches) and vagally innervated gastric mucosal septal pouches (Pavlov-type pouches). The secretagogues were always given by continuous i.v. infusion to produce steady states of secretory activity in the fasted conscious dogs; the antagonists were given by either rapid "bolus" i.v. injection or continuous i.v. infusion. With bolus injections, both antagonists promptly inhibited the secretion produced by histamine and its methyl derivatives. When control secretory rates were similar, 40 mumol of burimamide per kg and 4 mumol of metiamide per kg produced the same degree of inhibition. When the antagonists were also given by continuous i.v. infusion, the difference between them was greater, metiamide being 15 to 17 times more potent than burimamide. The effectiveness of the antagonists was not changed by vagal denervation. Symptoms of toxicity to burimamide developed at doses in excess of 30 mumol/kg/hr; none occurred with doses of metiamide ranging from 1.8 to 7.5 mumol/kg/hr.
本研究旨在确定在迷走神经切断的（海登海因小胃）和有迷走神经支配的胃黏膜隔小胃（巴甫洛夫型小胃）的犬中，甲氰咪胍和甲硫咪特作为组胺及其甲基衍生物Nα-甲基组胺、N-α，N-α-二甲基组胺和4-甲基组胺刺激胃酸分泌的拮抗剂的相对有效性。促分泌剂总是通过静脉连续输注给予，以使禁食清醒犬的分泌活动达到稳定状态；拮抗剂通过快速“推注”静脉注射或静脉连续输注给予。通过推注注射，两种拮抗剂均能迅速抑制组胺及其甲基衍生物产生的分泌。当对照分泌率相似时，每千克40微摩尔甲氰咪胍和每千克4微摩尔甲硫咪特产生相同程度的抑制。当拮抗剂也通过静脉连续输注给予时，它们之间的差异更大，甲硫咪特的效力比甲氰咪胍强15至17倍。迷走神经切断术并未改变拮抗剂的有效性。甲氰咪胍超过30微摩尔/千克/小时的剂量会出现毒性症状；甲硫咪特1.8至7.5微摩尔/千克/小时的剂量未出现毒性症状。
