NESS-0327 is a drug used in scientific research which acts as an extremely potent and selective
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
of the
cannabinoid receptor
Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recepto ...
CB1. It is much more potent an antagonist, and more selective for the CB
1 receptor over CB
2, than the more commonly used ligand
rimonabant
Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) is an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in t ...
, with a
Ki at CB
1 of 350fM (i.e. 0.00035nM) and a selectivity of over 60,000x for CB
1 over CB
2.
Independently, two other groups have described only modest nanomolar CB
1 affinity for this compound (125nM and
18.4nM).
Also unlike rimonabant, NESS-0327 does not appear to act as an
inverse agonist
In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.
A neutral antagonist has no activity in the absence of an agonist or inverse agon ...
at higher doses, instead being a purely
neutral antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...
which blocks the CB
1 receptor but does not produce any physiological effect of its own.
See also
*
Discovery and development of Cannabinoid Receptor 1 Antagonists
A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include ...
*
NESS-040C5
NESS-040C5 is a potent cannabinoid agonist which was developed for the treatment of glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle ...
References
Cannabinoids
CB1 receptor antagonists
Hydrazides
Chloroarenes
Pyrazoles
Piperazines
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