Receptor binding studies of soft anticholinergic agents

Fenglei Huang, Peter Buchwald, Clinton E. Browne, Hassan H. Farag, Whei Mei Wu, Fubao Ji, Guenther Hochhaus, Nicholas Bodor

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Receptor binding studies were performed on 24 soft anticholinergic agents and 5 conventional anticholinergic agents using 4 cloned human muscarinic receptor subtypes. The measured pKi values of the soft anticholinergic agents ranged from 6.5 to 9.5, with the majority being in the range of 7.5 to 8.5. Strong correlation was observed between the pKi s determined here and the pA2 values measured earlier in guinea pig ileum contraction assays. The corresponding correlation coefficients (r2 ) were 0.80, 0.73, 0.81, and 0.78 for pKi (m1 ), pKi (m2 ), pKi (m3 ), and pKi (m4 ), respectively. Quantitative structure-activity relationship (QSAR) studies were also performed, and good characterization could be obtained for the soft anticholinergics containing at least 1 tropine moiety in their structure. For these compounds, the potency as measured by the pKi values was found to be related to geometric, electronic, and lipophilicity descriptors. A linear regression equation using ovality (Oe), dipole moment (D), and a calculated log octanol-water partition coefficient (QLogP) gave reasonably good descriptions (r = 0.88) for the pKi (m3 ) values.

Original languageEnglish (US)
JournalAAPS PharmSci
Volume3
Issue number4
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • Antagonists
  • Drug design
  • Drug evaluation
  • Metabolism
  • Muscarinic
  • Receptor binding
  • Soft drugs

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Huang, F., Buchwald, P., Browne, C. E., Farag, H. H., Wu, W. M., Ji, F., Hochhaus, G., & Bodor, N. (2001). Receptor binding studies of soft anticholinergic agents. AAPS PharmSci, 3(4). https://doi.org/10.1208/ps030430