N-Methyl-beta-carboline-3-carboxamide (FG7142), an anxiogenic agent in the environment and evaluation of its exposure level in humans

N-甲基-β-咔啉-3-甲酰胺（FG7142），一种环境中的致焦虑剂及其在人体中的暴露水平评估

• 批准号: 07457093
• 负责人: MANABE Shigeo
• 金额: $ 4.74万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457093/
• 关键词: anxiogenic agent; beta-carboline; cigarette smoke; airborne particles; air pollution

FG 7142 (N-methyl-beta-carboline-3-carboxamide) is an anxiogenic agent used to investigate the pathogenesis and mechanism of anxiety in man. FG 7142, classified as a partial inverse agonist at benzodiazepine receptors, produces not only a strong anxiety-like syndrome in experimental animals, but also severe anxiety in man. This project is focused on the distribution and formation mechanism of FG 7142 in the environment and also on the effect of FG 7142 in the environment on humans.We have clearly demonstrated the followings :(1) FG 7142 has been measured in cigarette smoke, airborne partcles, automobile-exhaust particles, incinerator ash, smoke condensate of tree leaves and cigarette-smoke polluted indoor air by high-performance liquid chromatography. This compound has been detected in cigarette smoke, airborne partcles, smoke condensate of tree leaves and cigarette-smoke polluted indoor air, but not in automobile-exhaust partcles, cigarette and tree leaves themselves.These findings su … More ggest that FG 7142 is widely distributed in the environment and that FG 7142 is likely to be formed through conbustion of plants.(2) FG 7142 has been detected in the smoke condensate of wood shavings which is collected by an automatic smoking mechine. However, this compound has not been detected in the methylene chloride extract of wood shavings themseleves. Moreover, the yield of FG 7142 in the smoke condensate has increased dose-dependently with the added amounts of tryptophan and beta-carbolines possessing a carboxylate moiety. These findings suggest that FG 7142 is formed during combustion of plants and that tryptophan and beta-carbolines possessing a carboxylate moiety are precursors of FG 7142 in wood smoke.(3) FG 7142 has been detected in human urine. Our data suggest that humans are exposed to FG 7142 and that smokers are exposed to higher levels of FG 7142 than non-smokers. Results of animal experiments suggest that FG 7142 which enters the blood-stream is excreted in the urine via the kidneys within 24 h in an unchanged form. Therefore, monitoring the level of FG 7142 in urine may be useful for monitoring the exposure level of FG 7142. Less

FG 7142（N-甲基-β-咔啉-3-甲酰胺）是一种用于研究人类焦虑症发病机制的致焦虑剂。FG 7142被归类为苯二氮卓类受体的部分反向激动剂，不仅在实验动物中产生强烈的焦虑样综合征，本项目主要研究FG 7142在环境中的分布、形成机制以及环境中FG 7142对人体的影响，（1）用高效液相色谱法测定了香烟烟雾、空气微粒、汽车尾气微粒、焚烧炉灰、树叶烟雾冷凝物和石棉烟雾污染的室内空气中的FG 7142。在香烟烟雾、空气颗粒物、树叶烟雾冷凝物和受香烟烟雾污染的室内空气中检测到了该化合物，而在汽车尾气颗粒物、香烟和树叶本身中未检测到该化合物。 ...更多信息 推测FG 7142在环境中分布广泛，可能是通过植物共生形成的。(2)在自动吸烟机收集的木屑烟雾冷凝物中检测到FG 7142。然而，在木屑本身的二氯甲烷提取物中未检测到该化合物。此外，烟雾冷凝物中FG 7142的产率随着色氨酸和具有羧酸酯部分的β-咔啉的添加量而呈剂量依赖性增加。这些研究结果表明，FG 7142是在植物燃烧过程中形成的，色氨酸和具有羧酸根部分的β-咔啉是木材烟雾中FG 7142的前体。(3)FG 7142已在人类尿液中检出。我们的数据表明，人类暴露于FG 7142，吸烟者比非吸烟者暴露于更高水平的FG 7142。动物实验结果表明，进入血液的FG 7142在24小时内以原型形式通过肾脏经尿液排泄。因此，监测尿液中FG 7142的水平可用于监测FG 7142的暴露水平。少

项目成果

S.Manabe et al.: "Age-related accumulation of i-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid in human lens" Exprimental Eye Research. 63. 179-186 (1996)

S. Manabe 等人：“人晶状体中 i-甲基-1,2,3,4-四氢-β-咔啉-3-羧酸的年龄相关积累”实验眼研究 63. 179-186 (1996) ）

J.Yuan and S.Manabe: "Evaluation of exposure level of FG7142,an anxiogenic agent in humans" Environmental Pollution. (印刷中). (1997)

J. Yuan 和 S. Manabe：“人类致焦虑剂 FG7142 的暴露水平评估”《环境污染》（出版中）。

Manabe, S.et al.: "N-Methyl-beta-carboline-3-carboxamide (FG 7142) : an anxiogenix agent cigarette smoke condensate and its mechanism of formation" Euviron.Pollut.89(3). 329-335 (1995)

Manabe, S.et al.：“N-甲基-β-咔啉-3-甲酰胺 (FG 7142)：一种抗焦虑剂香烟烟雾冷凝物及其形成机制”Euviron.Pollut.89(3)。

Yuan, J.and Manabe, S.: "The mechanism of FG 7142, an anxiogenic agent through combustion of wood" Euviron. Sci.4(4). 221-231 (1996)

Yuan, J. 和 Manabe, S.：“FG 7142（一种通过木材燃烧产生的焦虑剂）的机制”Euviron。

J.Yuan and s.Manabe: "The Mechanism of formation of FG7142,an anxiogenic agent through combustion of wood" Environmental Science. 4.4. 221-231 (1996)

J.Yuan 和 s.Manabe：“通过木材燃烧产生焦虑剂 FG7142 的形成机制”环境科学。