Description
AM251 is a cannabinoid 1 (CB
1) receptor 1 antagonist. It binds to CB
1 receptors in rat forebrain membrane preparations (K
i = 7.5 nM) and is selective over CB
2 receptors in mouse spleen preparations (K
i = 2,290 nM) in radioligand binding assays. AM251 inhibits GTPγS binding induced by the CB receptor agonist CP 55,940 in HEK293 cells expressing human CB
1 receptors (EC
50 = 8 nM). AM251 (10 mg/kg) decreases immobility time in the forced swim test in wild-type but not CB
1 receptor-deficient mice. It reduces fasting-induced food intake and body weight gain in mice when administered at a dose of 30 mg/kg. AM251 also induces GTPγS binding in HEK293 cells expressing the orphan receptor GPR55 (EC
50 = 39 nM) and potentiates GABA-induced GABA
A receptor currents (EC
50 = 0.4 μM). It prevents TGF-β1-induced epithelial-to-mesenchymal transition (EMT), inhibits SMAD2/3 and p38 MAPK activation, and reduces the expression of EMT-related transcription factors in HK-2 renal tubule epithelial cells. AM251 induces cell cycle arrest at the G
2/M phase and apoptosis in A375 human melanoma cells.
Chemical Properties
White to Off-White Solid
Uses
Inhibitor of CB1 receptors. AM 251is a biarylpyrazole compound which has been considered for many years as the prototypical cannabinoid (CB) receptor antagonist
Uses
AM251, a CB
1 cannabinoid receptor antagonist, has been used in a study to determine its interaction with hippocampal neurons to enhance spatial memory in mice.
Definition
ChEBI: AM-251 is a carbohydrazide obtained by formal condensation of the carboxy group of 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid with the amino group of 1-aminopiperidine. An antagonist at the CB1 cannabinoid receptor. It has a role as a CB1 receptor antagonist, an apoptosis inducer, an antidepressant and an antineoplastic agent. It is a member of pyrazoles, a dichlorobenzene, an organoiodine compound, an amidopiperidine and a carbohydrazide.
Biological Activity
Potent CB 1 receptor antagonist (IC 50 = 8 nM, K i = 7.49 nM) that displays 306-fold selectivity over CB 2 receptors. Also potent GPR55 agonist (EC 50 = 39 nM). Also available as part of the Cannabinoid CB 1 Receptor Tocriset™ .
Biochem/physiol Actions
AM251 is a CB1 cannabinoid receptor antagonist.
References
[1] S.JOHN GATLEY . 123I-labeled AM251: a radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors[J]. European journal of pharmacology, 1996, 307 3: Pages 331-338. DOI:
10.1016/0014-2999(96)00279-8[2] S JOHN GATLEY . Binding of the non-classical cannabinoid CP 55,940, and the diarylpyrazole AM251 to rodent brain cannabinoid receptors[J]. Life sciences, 1997, 61 14: Pages PL191-PL197. DOI:
10.1016/s0024-3205(97)00690-5[3] PERTWEE R G. Inverse agonism and neutral antagonism at cannabinoid CB1 receptors[J]. Life sciences, 2005, 76 12: Pages 1307-1324. DOI:
10.1016/j.lfs.2004.10.025[4] L P SHEARMAN. Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice.[J]. Behavioural Pharmacology, 2003, 14 8: 573-582. DOI:
10.1097/00008877-200312000-00001[5] E RYBERG. The orphan receptor GPR55 is a novel cannabinoid receptor[J]. British Journal of Pharmacology, 2009, 152 7: 1092-1101. DOI:
10.1038/sj.bjp.0707460
