183232-66-8

AM251 is a cannabinoid 1 (CB₁) receptor 1 antagonist. It binds to CB₁ receptors in rat forebrain membrane preparations (K_i = 7.5 nM) and is selective over CB₂ 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 CB₁ receptors (EC₅₀ = 8 nM). AM251 (10 mg/kg) decreases immobility time in the forced swim test in wild-type but not CB₁ 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 (EC₅₀ = 39 nM) and potentiates GABA-induced GABA_A receptor currents (EC₅₀ = 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 G₂/M phase and apoptosis in A375 human melanoma cells.

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Inhibitor of CB1 receptors. AM 251is a biarylpyrazole compound which has been considered for many years as the prototypical cannabinoid (CB) receptor antagonist

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.

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™ .

AM251 is a CB1 cannabinoid receptor antagonist.

This CB1 inverse agonist (FW = 555.24 g/mol; CAS 183232-66-8; Solubility: 100 mM in DMSO; Fluorescent Derivative: Tocrifluor T1117), also named 1- (2,4-dichlorophenyl) -5- (4-iodophenyl) -4-methyl-N- (1- piperidyl) pyrazole-3-carboxamide, binds to the cannabinoid-1 receptor, potently blocking (Ki = 7.5 nM; IC50 = 8 nM) the action of endocannabinoids (See Anandamide). AM251 potentiates the forskolin- stimulated accumulation of cAMP, and it reduces the basal levels of inositol phosphate production in cells expressing the CB2 receptors. Such findings demonstrate that AM251 acts as inverse agonists at the human CB2 receptor acting via pathways coupled to members of the Ga family of GPCRs.

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1) Gatley et al. (1996), 123I-labeled AM251: a radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors; Eur. J. Pharmacol., 307 331 2) Gatley et al. (1997), Binding of the non-classical cannabinoid CP 55,940 and the diarylpyrazole AM251 to rodent brain cannabinoid receptors; Life Sci., 61 191 3) Pertwee et al. (2005), Inverse agonism and neutral antagonism at cannabinoid CB1 receptors; Life Sci., 76 1307 4) Shearman et al. (2003), Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse agonist AM251 in mice; behave. Pharmacol., 14 573 5) Ryberg et al. (2007), The orphan receptor GPR55 is a novel cannabinoid receptor; Br. J. Pharmacol., 152 1092