Histamine receptors represent a tried and tested target for the treatments of various conditions including allergic responses, gastric ulcers and dyspepsia. The eagerly awaited new generation of histamine H 3 antagonists looks set to represent a new class of potential blockbuster drugs.

Antagonists of the histamine H 1 and H 2 receptors have been successful as blockbuster drugs for treating allergic conditions and gastric ulcers, respectively. As such, histamine receptors have made a significant contribution to establishing G-protein-coupled receptors as the favored drug targets of the industry. In this light, it can easily be understood that the discovery of a third histamine receptor subtype (H 3 R) in 1983 was greeted with considerable excitement. However, characterization of the H 3 R turned out to be far from trivial. In the past five years, molecular biology approaches have given fresh impetus to the H 3 R research field. As a result, H 3 R ligands are where they were anticipated to be 20 years ago: at the center of attention and on the verge of an anticipated breakthrough as the next generation of histaminergic blockbuster drugs. Here, we assess the status of the H 3 R medicinal chemistry programs of the various players in the field, as far as can be deduced from patent applications and scientific literature.