Recent advances in histamine H3/H4 receptor ligands

Advances in molecular biology have brought fresh impetus to the field of research into histamine receptor ligands with the recent cloning of human histamine H₃ and H₄ receptors. Numerous promising potential therapeutic targets have been suggested for H₃ receptor ligands based on various pharmacological investigations, e.g., Alzheimer’s disease, schizophrenia, obesity, epilepsy, inflammatory diseases, sleep disorders and attention-deficit hyperactivity disorder. Concurrent to the availability of the receptors, the number of leads has also largely increased in the last few years, with some hybrid compounds acting simultaneously at two targets. In particular, the large number of different non-imidazole H₃ receptor antagonists possessing high affinities and selectivities and the first compound in clinical testing raise the hope for having a drug available in the market in the near future. The first studies with H₄ receptor ligands show promising anti-inflammatory and immunomodulatory properties.