WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 510338
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.
MedKoo Cat#: 510338
Name: AM251
CAS#: 183232-66-8
Chemical Formula: C22H21Cl2IN4O
Exact Mass: 554.01371
Molecular Weight: 555.24
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
| 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 | 36.38 | 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: 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. PubMed PMID: 25447325.
2: Ren Y, Wang J, Xu PB, Xu YJ, Miao CH. Systemic or intra-amygdala infusion of an endocannabinoid CB1 receptor antagonist AM251 blocked propofol-induced anterograde amnesia. Neurosci Lett. 2015 Jan 1;584:287-91. doi: 10.1016/j.neulet.2014.11.001. Epub 2014 Nov 6. PubMed PMID: 25445359.
3: 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. PubMed PMID: 25188001; PubMed Central PMCID: PMC4237656.
4: 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. PubMed PMID: 24801769; PubMed Central PMCID: PMC4149486.
5: 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. PubMed PMID: 23066093; PubMed Central PMCID: PMC3533472.
6: Aydin C, Oztan O, Isgor C. Nicotine-induced anxiety-like behavior in a rat model of the novelty-seeking phenotype is associated with long-lasting neuropeptidergic and neuroplastic adaptations in the amygdala: effects of the cannabinoid receptor 1 antagonist AM251. Neuropharmacology. 2012 Dec;63(8):1335-45. doi: 10.1016/j.neuropharm.2012.08.016. Epub 2012 Aug 31. PubMed PMID: 22959963; PubMed Central PMCID: PMC3697052.
7: Naderi N, Majidi M, Mousavi Z, Khoramian Tusi S, Mansouri Z, Khodagholi F. The interaction between intrathecal administration of low doses of palmitoylethanolamide and AM251 in formalin-induced pain related behavior and spinal cord IL1-β expression in rats. Neurochem Res. 2012 Apr;37(4):778-85. doi: 10.1007/s11064-011-0672-2. Epub 2011 Dec 27. PubMed PMID: 22201038.
8: Bialuk I, Winnicka MM. AM251, cannabinoids receptors ligand, improves recognition memory in rats. Pharmacol Rep. 2011;63(3):670-9. PubMed PMID: 21857077.
9: 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. Review. PubMed PMID: 21740450.
10: Dono LM, Currie PJ. The cannabinoid receptor CB₁ inverse agonist AM251 potentiates the anxiogenic activity of urocortin I in the basolateral amygdala. Neuropharmacology. 2012 Jan;62(1):192-9. doi: 10.1016/j.neuropharm.2011.06.019. Epub 2011 Jul 1. PubMed PMID: 21736884.
