Is an Inhibitor of Histamine-Forming Enzyme a New Type of "Anti-histamine" ?

α-氟甲基组氨酸（FMH）是L-组氨酸脱羧酶（HDC）的特异性抑制剂，HDC是一种组胺形成酶。本研究的目的如下：（1）FMH给药引起的组胺耗竭作为治疗组胺引起的病理状态的药物是否有效？(2)组胺耗竭是否会引起严重的副作用，因为组胺在各种生理状态中发挥作用？FMH能显著抑制纳氏乳鼠胃类癌组织中组胺的产生，并能完全保护胃类癌组织中过量产酸引起的消化性溃疡的形成。此外，FMH抑制异食癖反应，高岭土摄入反应后，双旋转刺激大鼠，这是一个模型的运动病。根据（2），豚鼠长期服用FMH引起的组胺耗竭并没有改变组胺H_1和H_2受体的敏感性，这是由[3 H]-美托咪胺结合和cAMP产生的微小变化来判断的。 ...更多信息 作为化学标记，回肠和心房的收缩分别作为生理反应。在小鼠和大鼠的一般药理学筛选试验中，除较高剂量（大于100 mg/kg）外，未观察到明显的作用。然而，进一步研究其对中枢神经系统的影响，FMH对血浆皮质酮和ACTH浓度的昼夜节律或睡眠觉醒的影响不大，并推迟了自发行为和饮酒行为的自由运行节律的相位。FMH对二硝基苯氟苯引起的豚鼠皮肤抗体形成和接触性过敏反应的调节作用也无明显影响。药代动力学分析表明，静脉注射FMH不易进入脑、胃和肝脏，但能迅速从肾脏排出，为今后的研究提供了依据。总之，FMH可能是治疗胃溃疡或运动病的有效药物，组胺耗竭不会引起严重的副作用，但仍需进一步研究。少

a-Fluoromethylhistidine (FMH) is a specific inhibitor of L-histidine decarboxylase (HDC), a histamine-forming enzyme. The purpose of this study is as follows (1) Is histamine depletion caused by administration of FMH effective as drugs for pathological conditions for which histamine is responsible? (2) Does the histamine depletion evoke serious side effects, beacause histamine plays roles in various physiological states? In terms of (1), FMH strogly inhibited the histamine production in gastric carcinoid of Mastomys natalensis and completely protected peptic ulcer formation caused by excess acid production. Also FMH inhibited a pica reaction, a kaolin intake response after double rotation stimutation in rats, which is a model of motion sickness. In terms of (2), histamine depletion caused by long-term administration of FMH in guinea-pigs did not change the sensitivity of histamine H_1 and H_2 receptors, as judged by the insignificant changes in [3H]-mepyramine binding and cAMP producti … More on as chemical markers, and contractions of the ileum and atrium as physiological responses, respectively. in screening test of general pharmacology of FMN in mice and rats, no significan effects were observed except in higher doses (greater than 100 mg/kg). On closer examination of its effect on CNS, however, FMH affected a little in the circadian rhythms of plasma concentrations of corticosteron and ACTH or sleep-awakeness, and retarded the phase of free-run rhythms of spontaneous and drinking behaviors. FMH also did not affect the regulation of immune responses like antibody formation and contact sensitivity reaction in the skin caused by dinitrophenylfluorobenzene in guinea-pigs. The pharmacokinetical analysis showed that FMH administered i.v. was not easily transported into the brain, stomach and liver, but rapildy rapidly excreted from the kidney, giving the basis for future studies. To sum up, the possiblity was demonstrated that FMH might be useful as a drug f or pep-tic ulcer or motion sickness and histamine depletion did not cause serious side effects, although further studies will be required. Less