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Front Cover: The Discovery of LML134, a Histamine H3 Receptor Inverse Agonist for the Clinical Treatment of Excessive Sleep Disorders (ChemMedChem 13/2019)
Author(s) -
Troxler Thomas,
Feuerbach Dominik,
Zhang Xuechun,
Yang Charles R.,
Lagu Bharat,
Perrone Mark,
Wang TieLin,
Briner Karin,
Bock Mark G.,
Auberson Yves P.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900365
Subject(s) - inverse agonist , agonist , narcolepsy , wakefulness , pharmacology , medicine , sleep (system call) , sleep deprivation , pharmacokinetics , histamine h3 receptor , neuroscience , receptor , psychology , modafinil , psychiatry , electroencephalography , computer science , circadian rhythm , operating system
The Front Cover shows the therapeutic effect of the H3 receptor inverse agonist LML134 ( 18b ), as expected in narcoleptic patients. Compound 18b results from an extensive optimization of safety and pharmacokinetic properties of several chemical series. It was selected for its ability to achieve high receptor occupancy in the brain within a short time frame, followed by fast target disengagement. This profile was designed to increase wakefulness during the day and help re‐establish a normal sleep pattern, without the risk of mechanism‐related insomnia during the night following drug administration. Compound 18b completed Phase I studies, and is undergoing further clinical trials to confirm its wakefulness‐promoting effect in patients suffering from shift‐work disorder. More information can be found in the Full Paper by Yves P. Auberson et al. on page 1238 in Issue 13, 2019 (DOI: 10.1002/cmdc.201900176).