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, ri ...

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 recep ...

CB₁. It is much more potent an antagonist, and more selective for the CB₁ receptor over CB₂, 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trade names Acomplia, Zimulti) is an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in t ...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 K_i at CB₁ of 350fM (i.e. 0.00035nM) and a selectivity of over 60,000x for CB₁ over CB₂. Independently, two other groups have described only modest nanomolar CB₁ 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 ago ...

at higher doses, instead being a purely neutral antagonist which blocks the CB₁ receptor but does not produce any physiological effect of its own.

References

Cannabinoids CB1 receptor antagonists Hydrazides Chloroarenes Pyrazoles Piperazines {{cannabinoid-stub

See also

References