Cipralisant (GT-2331, tentative trade name Perceptin) is an extremely potent
histamine H3 receptor ligand originally developed by Gliatech. Cipralisant was initially classified as a selective H
3 antagonist,
but newer research (2005) suggests also
agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
properties, i. e.
functional selectivity
Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...
.
Cipralisant seemed to be well tolerated during early testing, entering Phase II trials for
ADHD in 2000.
[Evaluate group]
Gliatech Announces Initiation of Perceptin Phase II Clinical Trial
The relatively recent cloning of human H
3 receptor, as well as the discovery of its constitutive activity provided the ability to better assess the activity of H
3 receptor ligands. Consequently, cipralisant was reassessed as an H
3 receptor agonist in human and rat recombinant systems, showing
functional selectivity
Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...
and stimulating one type of
G-protein coupled pathway while failing to activate other intracellular pathways.
Gliatech filed for bankruptcy in 2002, and its intellectual property was inherited by
Merck. The development of cipralisant seems to have been suspended since 2003 but research is ongoing, and recently it has been shown that it is the (1''S'',2''S'')-enantiomer which is the biologically active one.
References
Cyclopropanes
Histamine agonists
Imidazoles
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