Delineation of Receptor‐Ligand Interactions at the Human Histamine H 1 Receptor by a Combined Approach of Site‐Directed Mutagenesis and Computational Techniques – or – How to Bind the H 1 Receptor

Histamine H 1 antagonists or “antihistamines” are one of the most prescribed drug families in Western countries. They exert their effect by binding to the histamine H 1 receptor, a receptor belonging to the class of rhodopsin‐like G protein‐coupled receptors (GPCRs). In this review, the binding of ligands to the human histamine H 1 receptor with respect to site‐directed mutagenesis studies and molecular modeling techniques is described. The ligands described include agonists (histamine and histapro difens), a stereoselective partial agonist (lisuride), and selected inverse agonists (mepyramine, acrivastine and triprolidine).