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

组胺形成酶抑制剂是新型“抗组胺药”吗？

基本信息

批准号：
61870012
负责人：
MAEYAMA Kazutaka
金额：
$ 13.44万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

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

A-氟甲基组织（FMH）是一种特异性抑制剂，是一种组胺形成酶的L-抗二烷型脱羧酶（HDC）。这项研究的目的如下（1）是组胺耗竭是由施用的FMH施用作为病理疾病的药物的施用引起的？（2）组胺耗竭会引起严重的副作用，比起组胺在各种物理状态下起作用吗？就（1）而言，FMH串扰抑制了乳腺豆菌的胃癌的组胺产生，并完全保护了由过量酸产生引起的消化性溃疡形成。 FMH还抑制了PICA反应，这是大鼠双旋转刺激后的高岭土摄入反应，这是运动疾病的模型。在（2）方面，豚鼠中FMH长期给药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[3H] - 雌激素 - 米皮胺结合的无关紧要的变化和cAMP Products and Camp Products的微不足道的变化所判断的……在化学标志物，化学标志物和乳房中的质量更大。在小鼠和大鼠FMN一般药理学的筛查测试中，除了较高剂量（大于100 mg/kg）外，没有观察到显着影响。然而，在仔细研究其对中枢神经系统的影响时，FMH在血浆浓度的皮质蛋白酶和ACTH或ACTH或睡眠的昼夜节律上有所影响，并阻碍了赞助和饮酒行为的自由节奏的阶段。 FMH也不影响豚鼠二硝基氟氟苯引起的皮肤中的抗体形成和接触敏感反应等免疫反应的调节。药代动力学分析表明，FMH给药了。不容易将其转移到大脑，摊位和肝脏中，但是肾脏迅速超过了肾脏，为将来的研究提供了基础。总而言之，可能性证明，FMH可能是一种药物FMH或疾病，组胺耗竭并没有引起严重的副作用，尽管需要进一步的研究，但需要进一步研究。较少的