| Co-Investigator(Kenkyū-buntansha) |
長田 久美子 兵庫医科大学, 助手 (90068502)
YAMATODANI Atsushi Osaka University Medical School, 医学部, 助教授 (30116123)
MATSUNAGA Tohru Osaka University Medical School, 医学部, 教授 (10101271)
ONODERA Kenji Tohoku University School of Dentistry, 歯学部, 助手 (40133988)
WATANABE Takehiko Tohoku University School of Medicine, 医学部, 教授 (70028356)
KAWAGUCHI-NAGATA Kumiko Hyogo Medical College
|
|---|
| Research Abstract |
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
|
