›› 2011, Vol. 31 ›› Issue (4): 406-.doi: 10.3969/j.issn.1674-8115.2011.04.005

• Original article (Basic research) • Previous Articles     Next Articles

Separation of four stereoisomers of anisodamine and comparison of their anticholinergic activity

SUN Kai, XIE Yi-fan, CUI Yong-yao, CHEN Hong-zhuan, LU Yang, YANG Li-min   

  1. Department of Pharmacy, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2011-04-28 Published:2011-04-28
  • Supported by:

    Shanghai Education Committee Foundation, 06BZ009；Shanghai Science and Technology Committee Foundation, 06DZ19001

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Abstract:

Objective To investigate the relationship between stereoisomerism and pharmacological activity of anisodamine. Methods Two racemates of anisodamine （Ⅰand Ⅱ） were separated from synthetic anisodamine using MDS-5 column, and four stereoisomers of anisodamine were separated fromⅠ and Ⅱby high performance liquid chromatography using CHIRALPAK AD-H. The anticholinergic activities of four stereoisomers were compared by their inhibitory effects on carbachol-induced contractions of isolated rat tracheal smooth muscle. Results The absolute configurations of four stereoisomers were assigned using 1H NMR chemical shifts and specific rotation values. The difference of anticholinergic activities was observed among the four isomers of anisodamine. The order of potency was （6S, 2-S）＞（6S, 2-R）＞（6R, 2-S）＞（6R, 2-R）. Conclusion (S) configuration at the tropane ring plays more important role in the anticholinergic activity of anisodamine.

Key words: anisodamine, stereoisomers, tracheal smooth muscle