Structure of the human histamine H1 receptor complex with doxepin.

The common antihistamines are antagonists of histamine H1 receptor (H1R), a G-protein-coupled receptor (GPCR) that is expressed in various tissues including airway, intestinal smooth muscle and brain. The X-ray crystal structure of human H1R in the presence of doxepin, a first-generation H1R antagonist, is now reported. It shows that the drug resides in a much deeper pocket than in other aminergic GPCR structures. Analysis of drugprotein interactions should facilitate the development of antihistamines that are more selective and less likely to cause side effects than those currently available.