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

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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