Recent advances in histamine H3 receptor antagonists/inverse agonists.
BACKGROUND
Histamine H(3) receptor (H(3)R) 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 H(3)R ligands.


METHODS
A review was conducted of recent advances in the search for H(3)R antagonists/inverse agonists as reflected by patent applications/patents over the last 3 years.


RESULTS
A total of around 100 patent applications/patents along with selected peer-reviewed publications are surveyed. These involve antagonists/inverse agonists of H(3)R, 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.


CONCLUSIONS
Several H(3)R 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.
Łazewska
Dorota
D
Jagiellonian University Medical College, Department of Technology and Biotechnology of Drugs, Kraków, Poland.
Kieć-Kononowicz
Katarzyna
K
D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D054314:Drug Inverse Agonism; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D006801:Humans; D010330:Patents as Topic; D018100:Receptors, Histamine H3 / Q000187:drug effects* / Q000378:metabolism
D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3