The binding of arylguanidines at 5-HT(3) serotonin receptors: a structure-affinity investigation

Bioorg Med Chem Lett. 2001 Jun 18;11(12):1599-603. doi: 10.1016/s0960-894x(01)00291-8.

Abstract

The 5-HT(3) receptor binding affinities of nine pairs of aryl-substituted arylguanidines and arylbiguanides were examined and the results suggest the likelihood that both classes of agents utilize common receptor binding features. The effects of structural modification were also examined using CoMFA. 1-(3,4,5-Trichlorophenyl)guanidine (5-HT(3) K(i)=0.7 nM) was identified as a very high-affinity arylguanidine. The structures of the high-affinity arylguanidines are inconsistent with current 5-HT(3) pharmacophore models.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Guanidines / chemistry
  • Guanidines / metabolism*
  • Hybrid Cells
  • Mice
  • Models, Molecular
  • Protein Binding
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / chemistry
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / metabolism
  • Serotonin Receptor Agonists / chemistry
  • Serotonin Receptor Agonists / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Tumor Cells, Cultured

Substances

  • Guanidines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Serotonin Receptor Agonists