AM-251 is an inverse agonist at the CB₁

cannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

receptor. AM-251 is structurally very close to

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trade names Acomplia, Zimulti) is an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in t ...

; both are biarylpyrazole

cannabinoid receptor antagonist 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 includ ...

s. In AM-251, the ''p''- chloro group attached to the

phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...

substituent at C-5 of the

pyrazole Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazole is a weak base, with p''K''b 11.5 ( ...

ring is replaced with a ''p''- iodo group. The resulting compound exhibits slightly better

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a m ...

for the CB₁ receptor (with a K_i value of 7.5 nM) than rimonabant, which has a K_i value of 11.5 nM, AM-251 is, however, about two-fold more selective for the CB₁ receptor when compared to rimonabant. Like rimonabant, it is additionally a μ-opioid receptor antagonist that attenuates analgesic effects. AM251 has shown an ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

'' antimelanoma activity against

pancreatic The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an endocr ...

and colon cancer cells.

References

CB1 receptor antagonists Piperidines Pyrazoles Hydrazides Iodoarenes Chloroarenes AM cannabinoids Pyrazolecarboxamides Mu-opioid receptor antagonists Antineoplastic drugs {{cannabinoid-stub

See also

References