Related Experiment Video
Updated: Jan 26, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
The Discovery of LML134, a Histamine H3 Receptor Inverse Agonist for the Clinical Treatment of Excessive Sleep
Thomas Troxler1, Dominik Feuerbach1, Xuechun Zhang2
1Novartis Institutes for BioMedical Research, Novartis Pharma AG, Klybeckstrasse 141, 4057, Basel, Switzerland.
Abstract:
Histamine H3 receptor (H3R) inverse agonists that have been in clinical trials for the treatment of excessive sleep disorders, have been plagued with insomnia as a mechanism-based side effect. We focused on the identification of compounds that achieve high receptor occupancy within a short time, followed by rapid disengagement from the receptor, a target profile that could provide therapeutic benefits without the undesired side effect of insomnia. This article describes the optimization work that led to the discovery of 1-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate (18 b, LML134).
Related Concept Videos
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Substance Use Disorders Affecting Sleep
Understanding the concepts of physical dependence,...
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
REM Sleep Behavior Disorder
RBD is significantly associated with...
Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

