Recent advances in histamine H-3 receptor antagonists/inverse agonists

Importance of the field: Histamine H-3 receptor (H3R) antagonists/inverse agonists can be therapeutically useful in the treatment of various CNS, metabolic syndrome and allergic disorders, and constitute an attractive target in the search for new drugs. However, several drug candidates have been rejected because of unwanted effects. There is, therefore, a strong need to develop new H3R ligands. Areas covered in this review: A review was conducted of recent advances in the search for H3R antagonists/inverse agonists as reflected by patent applications/patents over the last 3 years. What the reader will gain: A total of around 100 patent applications/patents along with selected peer-reviewed publications are surveyed. These involve antagonists/inverse agonists of H3R, which the authors have divided into five groups. The above-mentioned compounds were evaluated for their potential utility in the treatment of narcolepsy, attention deficit hyperactivity disorder, epilepsy, Alzheimer's disease, schizophrenia, obesity and neuropathic pain. Take home message: Several H3R antagonists/inverse agonists appear to be promising drug candidates, including at least 15 compounds undergoing evaluation in clinical development. Especially interesting is pitolisant, which is progressing through to Phase III clinical trials.