AM-251 (drug) explained

AM-251 is an inverse agonist at the CB₁ cannabinoid receptor. AM-251 is structurally very close to rimonabant; both are biarylpyrazole cannabinoid receptor antagonists. In AM-251, the p-chloro group attached to the phenyl substituent at C-5 of the pyrazole ring is replaced with a p-iodo group. The resulting compound exhibits slightly better binding affinity 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.^[1] Like rimonabant, it is additionally a μ-opioid receptor antagonist^[2] that attenuates analgesic effects.^[3]

AM251 has shown an in vitro antimelanoma activity against pancreatic and colon cancer cells.^[4]

See also

• Discovery and development of Cannabinoid Receptor 1 Antagonists

Notes and References

1. Lan R, Liu Q, Fan P, Lin S, Fernando SR, McCallion D, Pertwee R, Makriyannis A . 6 . Structure-activity relationships of pyrazole derivatives as cannabinoid receptor antagonists . Journal of Medicinal Chemistry . 42 . 4 . 769–776 . February 1999 . 10052983 . 10.1021/jm980363y .
2. Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL . AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid/cannabinoid interaction studies . Neuropharmacology . 63 . 5 . 905–915 . October 2012 . 22771770 . 3408547 . 10.1016/j.neuropharm.2012.06.046 .
3. Seely KA, Brents LK, Franks LN, Rajasekaran M, Zimmerman SM, Fantegrossi WE, Prather PL . AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid/cannabinoid interaction studies . Neuropharmacology . 63 . 5 . 905–915 . October 2012 . 22771770 . 3408547 . 10.1016/j.neuropharm.2012.06.046 .
4. Carpi S, Fogli S, Romanini A, Pellegrino M, Adinolfi B, Podestà A, Costa B, Da Pozzo E, Martini C, Breschi MC, Nieri P . 6 . AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells . Anti-Cancer Drugs . 26 . 7 . 754–762 . August 2015 . 25974027 . 10.1097/CAD.0000000000000246 . 11568/750318 . live . 205526223 . https://web.archive.org/web/20210702220857/https://arpi.unipi.it/retrieve/handle/11568/750318/395886/Post-Print_2015_Carpi%20Nieri%20Anti-Cancer%20Drugs.pdf . July 2, 2021 .