Hough L B, Jackowski S, Eberle N, Gogas K R, Camarota N A, Cue D
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
Biochem Pharmacol. 1988 Dec 15;37(24):4707-11. doi: 10.1016/0006-2952(88)90341-3.
The effects of zolantidine, the first brain-penetrating H2-receptor antagonist, on the brain levels of histamine (HA) and the HA metabolite tele-methylhistamine (t-MH), the activity of histamine methyltransferase (HMT) and the brain HA turnover rates were investigated in rats. Zolantidine dimaleate (0.1 to 100 mg/kg, s.c.) had no effect on whole brain levels of HA or t-MH and no effect on brain HMT activity, when measured 30 min after administration. Furthermore, brain t-MH levels in pargyline-treated animals were unaffected by zolantidine (0.1 to 25 mg/kg), indicating the absence of an effect on brain HA turnover. In vitro, zolantidine was a potent competitive inhibitor of both brain and kidney HMT, with Ki values of 2.3 and 2.7 microM respectively. These results show that, despite the ability of zolantidine to inhibit HMT in vitro, large doses of this drug did not alter brain HA methylation or turnover in vivo, and they imply that blockade of post-synaptic H2-receptors does not change brain HA dynamics.
研究了首个可穿透血脑屏障的H2受体拮抗剂佐兰替丁对大鼠脑内组胺（HA）水平、HA代谢物 tele -甲基组胺（t - MH）、组胺甲基转移酶（HMT）活性及脑内HA周转率的影响。给予马来酸佐兰替丁（0.1至100 mg/kg，皮下注射）后30分钟测量发现，其对全脑HA或t - MH水平以及脑HMT活性均无影响。此外，帕吉林处理的动物脑内t - MH水平不受佐兰替丁（0.1至25 mg/kg）影响，表明其对脑内HA周转率无作用。在体外，佐兰替丁是脑和肾HMT的强效竞争性抑制剂，其Ki值分别为2.3和2.7 microM。这些结果表明，尽管佐兰替丁在体外有抑制HMT的能力，但大剂量该药物在体内并未改变脑内HA甲基化或周转率，这意味着突触后H2受体的阻断不会改变脑内HA动态变化。
