183232-66-8 Usage
Description
AM251 is a cannabinoid 1 (CB1) receptor 1 antagonist. It binds to CB1 receptors in rat forebrain membrane preparations (Ki = 7.5 nM) and is selective over CB2 receptors in mouse spleen preparations (Ki = 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 GABAA 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.
Chemical Properties
White to Off-White Solid
Uses
Different sources of media describe the Uses of 183232-66-8 differently. You can refer to the following data:
1. AM251, a CB1 cannabinoid receptor antagonist, has been used in a study to determine its interaction with hippocampal neurons to enhance spatial memory in mice.
2. Inhibitor of CB1 receptors. AM 251is a biarylpyrazole compound which has been considered for many years as the prototypical cannabinoid (CB) receptor antagonist
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) 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
Check Digit Verification of cas no
The CAS Registry Mumber 183232-66-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,8,3,2,3 and 2 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 183232-66:
(8*1)+(7*8)+(6*3)+(5*2)+(4*3)+(3*2)+(2*6)+(1*6)=128
128 % 10 = 8
So 183232-66-8 is a valid CAS Registry Number.
InChI:InChI=1/C22H21Cl2IN4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-7-16(23)13-18(19)24)21(14)15-5-8-17(25)9-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)
183232-66-8Relevant articles and documents
A method for parallel solid-phase synthesis of Lodinated analogues of the CB1 receptor inverse agonist rimonabant
Spivey, Alan C.,Tseng, Chih-Chung,Jones, Teyrnon C.,Kohler, Andrew D.,Ellames, George J.
supporting information; experimental part, p. 4760 - 4763 (2009/12/27)
A method for the parallel solid-phase synthesis (SPS) of iodinated analogues of Sanofi-Aventis' type 1 cannabinoid (CB1) receptor Inverse agonist rimonabant (acomplia) has been developed. The method allows the synthesis of a range of C3 amide/hydrazide derivatives from a resin-bound C3 ester precursor. The C-Ge linkage to the Hypogel-200 resin Is stable to the diversification conditions but allows ipsoiododegermylative cleavage using Nal/NCS even for the products containing the oxidatively labile hydrazide moiety.
Preparation of iodine-123 labeled AM251: A potential spect radioligand for the brain cannabinoid CB1 receptor
Lan, Ruoxi,Gatley, S. John,Makriyannis, Alexandros
, p. 875 - 881 (2007/10/03)
We report the synthesis and labeling with iodine-123 of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole -3-carboxamide (AM251). This compound is an anlog of the recently described cannabinoid receptor antagonist, R141716A,
