| Identification of some benproperine metabolites in humans and investigation of their antitussive effect | |
| Alternative Title | Identification of some benproperine metabolites in humans and investigation of their antitussive effect |
| Li Y1; Zhong DF1; Chen SW1; Maeba I1 | |
| 2005 | |
| Source Publication | ACTA PHARMACOLOGICA SINICA
 |
| ISSN | 1671-4083 |
| Volume | 26Issue:12Pages:1519-1526 |
| Abstract | 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. |
| Other Abstract | 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. |
| Keyword | ACID-INDUCED COUGH MECHANISMS benproperine metabolism antitussive agents hydroxylation glucuronide high performance liquid chromatography mass spectrometry |
| Indexed By | CSCD |
| Language | 英语 |
| CSCD ID | CSCD:2209851 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.imr.ac.cn/handle/321006/142869 |
| Collection | 中国科学院金属研究所 |
| Affiliation | 1.中国科学院金属研究所 2.名城大学 |
| Recommended Citation 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. |
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