Constitutive activity of the histamine H(1) receptor reveals inverse agonism of histamine H(1) receptor antagonists

Eur J Pharmacol. 2000 Jan 3;387(1):R5-7. doi: 10.1016/s0014-2999(99)00803-1.


Transient expression of the wild-type human histamine H(1) receptor in SV40-immortalised African green monkey kidney cells resulted in an agonist-independent elevation of the basal levels of the second messenger inositoltrisphospate. Several histamine H(1) receptor antagonists, including the therapeutically used anti-allergics cetirizine, loratadine and epinastine reduced this constitutive histamine H(1) receptor activity. Inverse agonism, i.e., stabilisation of an inactive conformation of the human histamine H(1) receptor, may therefore be a key component of the anti-allergic mechanism of action of clinically used antihistamines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • COS Cells
  • Cell Line, Transformed
  • Histamine / pharmacology
  • Histamine Agonists / metabolism
  • Histamine Agonists / pharmacology*
  • Histamine H1 Antagonists / metabolism
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Inositol Phosphates / metabolism
  • Methylhistidines / pharmacology
  • Pyrilamine / metabolism
  • Pyrilamine / pharmacology
  • Radioligand Assay
  • Receptors, Histamine H1 / drug effects*
  • Receptors, Histamine H1 / genetics
  • Receptors, Histamine H1 / metabolism
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism


  • Histamine Agonists
  • Histamine H1 Antagonists
  • Inositol Phosphates
  • Methylhistidines
  • Receptors, Histamine H1
  • Recombinant Fusion Proteins
  • alpha-fluoromethylhistidine
  • Histamine
  • Pyrilamine