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

1 Citation (Scopus)

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 pKis 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 (Oc), 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
JournalAAPS Journal
Volume3
Issue number4
StatePublished - Dec 1 2001
Externally publishedYes

Fingerprint

Cholinergic Antagonists
Octanols
Quantitative Structure-Activity Relationship
Muscarinic Receptors
Ileum
Linear Models
Guinea Pigs
Water

Keywords

  • Design
  • Drug
  • Drug evaluation
  • Metabolism
  • Muscarinic antagonists
  • Receptor binding
  • Soft drugs

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Huang, F., Buchwald, P., Browne, C. E., Farag, H. H., Wu, W. M., Ji, F., ... Bodor, N. (2001). Receptor Binding Studies of Soft Anticholinergic Agents. AAPS Journal, 3(4).

Receptor Binding Studies of Soft Anticholinergic Agents. / Huang, Fenglei; Buchwald, Peter; Browne, Clinton E.; Farag, Hassan H.; Wu, Whei Mei; Ji, Fubao; Hochhaus, Guenther; Bodor, Nicholas.

In: AAPS Journal, Vol. 3, No. 4, 01.12.2001.

Research output: Contribution to journalArticle

Huang, F, Buchwald, P, Browne, CE, Farag, HH, Wu, WM, Ji, F, Hochhaus, G & Bodor, N 2001, 'Receptor Binding Studies of Soft Anticholinergic Agents', AAPS Journal, vol. 3, no. 4.
Huang F, Buchwald P, Browne CE, Farag HH, Wu WM, Ji F et al. Receptor Binding Studies of Soft Anticholinergic Agents. AAPS Journal. 2001 Dec 1;3(4).
Huang, Fenglei ; Buchwald, Peter ; Browne, Clinton E. ; Farag, Hassan H. ; Wu, Whei Mei ; Ji, Fubao ; Hochhaus, Guenther ; Bodor, Nicholas. / Receptor Binding Studies of Soft Anticholinergic Agents. In: AAPS Journal. 2001 ; Vol. 3, No. 4.
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