Identification of some benproperine metabolites in humans and investigation of their antitussive effect

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	Identification of some benproperine metabolites in humans and investigation of their antitussive effect
其他题名	Identification of some benproperine metabolites in humans and investigation of their antitussive effect
	Li Y 1; Zhong DF 1; Chen SW 1; Maeba I 1
	2005
发表期刊	ACTA PHARMACOLOGICA SINICA
ISSN	1671-4083
卷号	26 期号:12 页码:1519-1526
摘要	Aim: To identify 4 unknown metabolites of benproperine (BPP, 1) in human urine after a po dose, and to investigate the antitussive effect of monohydroxylate metabolites. Methods: The putative metabolite references were prepared using chemical synthesis. Their structures were identified using H-1 and C-13 nuclear magnetic resonance, and mass spectrometry. The metabolites in human urine were separated and assayed using liquid chromatography-ion trap mass spectrometry (LC/MS/MS), and further confirmed by comparison of their mass spectra and chromatographic retention times with those of synthesized reference substances. The antitussive effects of metabolites were evaluated on coughs induced by 7.5% citric acid in conscious guinea pigs. Results: 1-1-Methyl-2-2-(phenylmethyl)phenoxy-ethyl-4-piperidinol (2), 1-1-methyl-2-2-(phenylmethyl) phenoxy ethyl-3-piperidinol (3) and their glucuronides 4 and 5 were obtained from chemical synthesis. Four urinary metabolites in human urine showed peaks with the same chromatographic retention times and mass spectra in LC/MS/MS as synthetic substances 2, 3, 4 and 5. Phosphates of compounds 2 and 3 prolonged the latency of cough and reduced the number of coughs during the 3 min test using citric acid, but did not reduce the number of coughs during the 5 min immediately after the test in conscious guinea pigs. Conclusion: Compounds 2, 3, 4, and 5 were identified as the metabolites of BPP in human urine. Among them, compounds 2 and 3 are inactive in the antitussive effect.
其他摘要	Aim： To identify 4 unknown metabolites of benproperine （BPE l） in human urine after a po dose, and to investigate the antitussive effect of monohydroxylate metabolites. Methods： The putative metabolite references were prepared using chemical synthesis. Their structures were identified using ^1H and ^13C nuclear magnetic resonance, and mass spectrometry. The metabolites in human urine were separated and assayed using liquid chromatography-ion trap mass spectrometry （LC/MS/MS）, and further confirmed by comparison of their mass spectra and chromatographic retention times with those of synthesized reference substances. The antitussive effects of metabolites were evaluated on coughs induced by 7.5% citric acid in conscious guinea pigs. Results： 1-1-Methyl-2-2- （phenylmethyl）phenoxy-ethyl -4-piperidinol （2）, 1 - 1-methyl-2- 2- （phenylmethyl） phenoxy ethyl-3-piperidinol （3） and their glucuronides 4 and 5 were obtained from chemical synthesis. Four urinary metabolites in human urine showed peaks with the same chromatographic retention times and mass spectra in LC/MS/MS as synthetic substances 2, 3, 4 and 5. Phosphates of compounds 2 and 3 prolonged the latency of cough and reduced the number of coughs during the 3 min test using citric acid, but did not reduce the number of coughs during the 5 rain imme- diately after the test in conscious guinea pigs. Conclusion： Compounds 2, 3, 4, and 5 were identified as the metabolites of BPP in human urine. Among them, compounds 2 and 3 are inactive in the antitussive effect.
关键词	ACID-INDUCED COUGH MECHANISMS benproperine metabolism antitussive agents hydroxylation glucuronide high performance liquid chromatography mass spectrometry
收录类别	CSCD
语种	英语
CSCD记录号	CSCD:2209851
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/142869
专题	中国科学院金属研究所
作者单位	1.中国科学院金属研究所 2.名城大学
推荐引用方式 GB/T 7714	Li Y,Zhong DF,Chen SW,et al. Identification of some benproperine metabolites in humans and investigation of their antitussive effect[J]. ACTA PHARMACOLOGICA SINICA,2005,26(12):1519-1526.
APA	Li Y,Zhong DF,Chen SW,&Maeba I.(2005).Identification of some benproperine metabolites in humans and investigation of their antitussive effect.ACTA PHARMACOLOGICA SINICA,26(12),1519-1526.
MLA	Li Y,et al."Identification of some benproperine metabolites in humans and investigation of their antitussive effect".ACTA PHARMACOLOGICA SINICA 26.12(2005):1519-1526.