WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H510338
CAS#: 183232-66-8
Description: AM251 is a cannabinoid receptor antagonist. AM251 improves recognition memory in rats and produces nocifensive behavior via activation of ERK signaling pathway. Moreover, AM251 alters mitochondrial physiology via proteolytic degradation of ERRα and attenuates mechanical allodynia and thermal hyperalgesia after burn injury.
Hodoodo Cat#: H510338
Name: AM251
CAS#: 183232-66-8
Chemical Formula: C22H21Cl2IN4O
Exact Mass: 554.01
Molecular Weight: 555.240
Elemental Analysis: C, 47.59; H, 3.81; Cl, 12.77; I, 22.86; N, 10.09; O, 2.88
Synonym: AM251; AM 251; AM-251.
IUPAC/Chemical Name: 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
InChi Key: BUZAJRPLUGXRAB-UHFFFAOYSA-N
InChi Code: InChI=1S/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)
SMILES Code: O=C(C1=NN(C2=CC=C(Cl)C=C2Cl)C(C3=CC=C(I)C=C3)=C1C)NN4CCCCC4
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | AM251 is a selective cannabinoid 1 (CB1) receptor antagonist with an IC50 of 8 nM, also acts as a potent GPR55 agonist with an EC50 of 39 nM. |
| In vitro activity: | However, TGF-β effect was inhibited in the presence of CB1 agonist ACEA 1 μM in association with CB1 selective antagonist AM251 10 μM (24.76 ± 6.43 vs 2.03 ± 0.87, P = 0.0451, statistically significant). Moreover, CB1 antagonist alone also prevented TGF-β effect on α-SMA expressions (24.76 ± 6.43 vs 1.74 ± 1.15, P = 0.0451, statistically significant). In this context, this study evaluated the effect of this drug at concentrations of 1 μM, 5 μM and 10 μM in the fibroblast primary culture activated with TGF-β. AM251 inhibited the TGF-β effect on α-SMA expression in a concentration-dependent manner (Fig. 4). This effect was significant at concentrations ≥1 μM (all P < 0.05vsTGF-β), reaching a maximum at the concentration of 5 μM. Reference: Eur J Pharmacol. 2021 Feb 5;892:173738. https://pubmed.ncbi.nlm.nih.gov/33220269/ |
| In vivo activity: | As anticipated, a 5 mg·kg−1, i.p. dose of CB‐13 induced hypothermia in ABH mice (Figure 1), which has been shown previously to be CB1 receptor‐mediated and completely absent in CB1 receptor‐deficient mice. This induced significant visible sedation and also induced hypothermia, which was measured to provide a quantitative readout. The hypothermic effect was rapidly antagonized with AM251 (5 mg·kg−1, i.v.; Figure 1), and the significant marked sedation, associated with the relative lack of motility, was lost within 20 min. The hypothermia was lost by 40 min after treatment with AM251 (Figure 1). Therefore, a CB1 receptor inverse agonist can reverse CB1 receptor‐mediated cannabimimetic effects. Reference: Br J Pharmacol. 2017 Nov; 174(21): 3790–3794. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647190/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 36.4 | 65.52 | |
| DMF | 10.0 | 18.01 | |
| Ethanol | 14.0 | 25.21 |
The following data is based on the product molecular weight 555.24 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Correia-Sá IB, Carvalho CM, Serrão PV, Machado VA, Carvalho SO, Marques M, Vieira-Coelho MA. AM251, a cannabinoid receptor 1 antagonist, prevents human fibroblasts differentiation and collagen deposition induced by TGF-β - An in vitro study. Eur J Pharmacol. 2021 Feb 5;892:173738. doi: 10.1016/j.ejphar.2020.173738. Epub 2020 Nov 19. PMID: 33220269. 2. Yoshinaga T, Uwabe K, Naito S, Higashino K, Nakano T, Numata Y, Kihara A. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells. PLoS One. 2016 Dec 9;11(12):e0167848. doi: 10.1371/journal.pone.0167848. PMID: 27936102; PMCID: PMC5148003. 3. Parihar VK, Syage A, Flores L, Lilagan A, Allen BD, Angulo MC, Song J, Smith SM, Arechavala RJ, Giedzinski E, Limoli CL. The Cannabinoid Receptor 1 Reverse Agonist AM251 Ameliorates Radiation-Induced Cognitive Decrements. Front Cell Neurosci. 2021 Jun 28;15:668286. doi: 10.3389/fncel.2021.668286. PMID: 34262437; PMCID: PMC8273551. 4. Pryce G, Baker D. Antidote to cannabinoid intoxication: the CB1 receptor inverse agonist, AM251, reverses hypothermic effects of the CB1 receptor agonist, CB-13, in mice. Br J Pharmacol. 2017 Nov;174(21):3790-3794. doi: 10.1111/bph.13973. Epub 2017 Sep 20. PMID: 28800377; PMCID: PMC5647190. |
| In vitro protocol: | 1. Correia-Sá IB, Carvalho CM, Serrão PV, Machado VA, Carvalho SO, Marques M, Vieira-Coelho MA. AM251, a cannabinoid receptor 1 antagonist, prevents human fibroblasts differentiation and collagen deposition induced by TGF-β - An in vitro study. Eur J Pharmacol. 2021 Feb 5;892:173738. doi: 10.1016/j.ejphar.2020.173738. Epub 2020 Nov 19. PMID: 33220269. 2. Yoshinaga T, Uwabe K, Naito S, Higashino K, Nakano T, Numata Y, Kihara A. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells. PLoS One. 2016 Dec 9;11(12):e0167848. doi: 10.1371/journal.pone.0167848. PMID: 27936102; PMCID: PMC5148003. |
| In vivo protocol: | 1. Parihar VK, Syage A, Flores L, Lilagan A, Allen BD, Angulo MC, Song J, Smith SM, Arechavala RJ, Giedzinski E, Limoli CL. The Cannabinoid Receptor 1 Reverse Agonist AM251 Ameliorates Radiation-Induced Cognitive Decrements. Front Cell Neurosci. 2021 Jun 28;15:668286. doi: 10.3389/fncel.2021.668286. PMID: 34262437; PMCID: PMC8273551. 2. Pryce G, Baker D. Antidote to cannabinoid intoxication: the CB1 receptor inverse agonist, AM251, reverses hypothermic effects of the CB1 receptor agonist, CB-13, in mice. Br J Pharmacol. 2017 Nov;174(21):3790-3794. doi: 10.1111/bph.13973. Epub 2017 Sep 20. PMID: 28800377; PMCID: PMC5647190. |
1: Raffa RB, Ward SJ. CB₁-independent mechanisms of Δ⁹-THCV, AM251 and SR141716 (rimonabant). J Clin Pharm Ther. 2012 Jun;37(3):260-5. doi: 10.1111/j.1365-2710.2011.01284.x. Epub 2011 Jul 11. PMID: 21740450.
2: Yoshinaga T, Uwabe K, Naito S, Higashino K, Nakano T, Numata Y, Kihara A. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells. PLoS One. 2016 Dec 9;11(12):e0167848. doi: 10.1371/journal.pone.0167848. PMID: 27936102; PMCID: PMC5148003.
3: O'Keefe L, Vu T, Simcocks AC, Jenkin KA, Mathai ML, Hryciw DH, Hutchinson DS, McAinch AJ. CB1 Ligand AM251 Induces Weight Loss and Fat Reduction in Addition to Increased Systemic Inflammation in Diet-Induced Obesity. Int J Mol Sci. 2022 Sep 28;23(19):11447. doi: 10.3390/ijms231911447. PMID: 36232744; PMCID: PMC9569643.
4: Correia-Sá IB, Carvalho CM, Serrão PV, Machado VA, Carvalho SO, Marques M, Vieira-Coelho MA. AM251, a cannabinoid receptor 1 antagonist, prevents human fibroblasts differentiation and collagen deposition induced by TGF-β - An in vitro study. Eur J Pharmacol. 2021 Feb 5;892:173738. doi: 10.1016/j.ejphar.2020.173738. Epub 2020 Nov 19. PMID: 33220269.
5: Carpi S, Fogli S, Romanini A, Pellegrino M, Adinolfi B, Podestà A, Costa B, Da Pozzo E, Martini C, Breschi MC, Nieri P. AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. Anticancer Drugs. 2015 Aug;26(7):754-62. doi: 10.1097/CAD.0000000000000246. PMID: 25974027.
6: Bialuk I, Winnicka MM. AM251, cannabinoids receptors ligand, improves recognition memory in rats. Pharmacol Rep. 2011;63(3):670-9. doi: 10.1016/s1734-1140(11)70578-3. PMID: 21857077.
7: Krzysik-Walker SM, González-Mariscal I, Scheibye-Knudsen M, Indig FE, Bernier M. The biarylpyrazole compound AM251 alters mitochondrial physiology via proteolytic degradation of ERRα. Mol Pharmacol. 2013 Jan;83(1):157-66. doi: 10.1124/mol.112.082651. Epub 2012 Oct 12. PMID: 23066093; PMCID: PMC3533472.
8: Tran S, Chatterjee D, Facciol A, Gerlai R. Concentration, population, and context-dependent effects of AM251 in zebrafish. Psychopharmacology (Berl). 2016 Apr;233(8):1445-54. doi: 10.1007/s00213-016-4240-y. Epub 2016 Feb 16. PMID: 26883874.
9: Ruz-Maldonado I, Liu B, Atanes P, Pingitore A, Huang GC, Choudhary P, Persaud SJ. The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling. Cell Mol Life Sci. 2020 Nov;77(22):4709-4723. doi: 10.1007/s00018-019-03433-6. Epub 2020 Jan 10. PMID: 31925452; PMCID: PMC7599183.
10: Patil M, Patwardhan A, Salas MM, Hargreaves KM, Akopian AN. Cannabinoid receptor antagonists AM251 and AM630 activate TRPA1 in sensory neurons. Neuropharmacology. 2011 Sep;61(4):778-88. doi: 10.1016/j.neuropharm.2011.05.024. Epub 2011 May 27. PMID: 21645531; PMCID: PMC3130079.
11: Ueda M, Iwasaki H, Wang S, Murata E, Poon KY, Mao J, Martyn JA. Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury. Anesthesiology. 2014 Dec;121(6):1311-9. doi: 10.1097/ALN.0000000000000422. PMID: 25188001; PMCID: PMC4237656.
12: Jenkin KA, O'Keefe L, Simcocks AC, Grinfeld E, Mathai ML, McAinch AJ, Hryciw DH. Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats. J Endocrinol. 2015 May;225(2):113-24. doi: 10.1530/JOE-15-0004. Epub 2015 Mar 24. PMID: 25804605.
13: de Oliveira Alvares L, Genro BP, Vaz Breda R, Pedroso MF, Da Costa JC, Quillfeldt JA. AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long-term potentiation and induces retrograde amnesia in rats. Brain Res. 2006 Feb 23;1075(1):60-7. doi: 10.1016/j.brainres.2005.11.101. Epub 2006 Feb 7. PMID: 16464439.
14: Liu J, Pope C. The cannabinoid receptor antagonist AM251 increases paraoxon and chlorpyrifos oxon toxicity in rats. Neurotoxicology. 2015 Jan;46:12-8. doi: 10.1016/j.neuro.2014.11.001. Epub 2014 Nov 20. PMID: 25447325; PMCID: PMC4448943.
15: Nazari M, Komaki A, Salehi I, Sarihi A, Shahidi S, Komaki H, Ganji A. Interactive effects of AM251 and baclofen on synaptic plasticity in the rat dentate gyrus. Brain Res. 2016 Nov 15;1651:53-60. doi: 10.1016/j.brainres.2016.09.029. Epub 2016 Sep 20. PMID: 27663967.
16: Lee YM, Uhm KO, Lee ES, Kwon J, Park SH, Kim HS. AM251 suppresses the viability of HepG2 cells through the AMPK (AMP-activated protein kinase)-JNK (c-Jun N-terminal kinase)-ATF3 (activating transcription factor 3) pathway. Biochem Biophys Res Commun. 2008 Jun 13;370(4):641-5. doi: 10.1016/j.bbrc.2008.04.003. Epub 2008 Apr 10. PMID: 18406347.
17: Katsuyama S, Mizoguchi H, Komatsu T, Nagaoka K, Sakurada S, Sakurada T. The cannabinoid 1 receptor antagonist AM251 produces nocifensive behavior via activation of ERK signaling pathway. Neuropharmacology. 2010 Nov;59(6):534-41. doi: 10.1016/j.neuropharm.2010.07.015. Epub 2010 Jul 21. PMID: 20654633.
18: Karimi SA, Noorbakhsh M, Komaki H, Reza Nikoo M, Hasanein P, Shahidi S, Faraji N, Komaki A. The interactive effects of verapamil and CB1 cannabinoid receptor antagonist/inverse agonist, AM251 on passive avoidance learning and memory in rat. Behav Pharmacol. 2022 Apr 1;33(2&3):222-229. doi: 10.1097/FBP.0000000000000638. PMID: 34845169.
19: Fiori JL, Sanghvi M, O'Connell MP, Krzysik-Walker SM, Moaddel R, Bernier M. The cannabinoid receptor inverse agonist AM251 regulates the expression of the EGF receptor and its ligands via destabilization of oestrogen-related receptor α protein. Br J Pharmacol. 2011 Oct;164(3):1026-40. doi: 10.1111/j.1476-5381.2011.01384.x. PMID: 21449913; PMCID: PMC3195923.
20: Ratano P, Everitt BJ, Milton AL. The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala. Neuropsychopharmacology. 2014 Oct;39(11):2529-37. doi: 10.1038/npp.2014.103. Epub 2014 May 7. PMID: 24801769; PMCID: PMC4149486.
