AM-251

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H21Cl2IN4O
Molecular Weight	555.239
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=CC=C(Cl)C=C3Cl)C4=CC=C(I)C=C4

InChI

InChIKey=BUZAJRPLUGXRAB-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C22H21Cl2IN4O
Molecular Weight	555.239
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9335234 | https://www.ncbi.nlm.nih.gov/pubmed/14665975 | https://www.ncbi.nlm.nih.gov/pubmed/23932644

AM-251 is a 123I radioisotope and potent CB1 receptor antagonist derivative of the CB1 cannabinoid receptor inverse agonist SR141716A, presenting a radioprobe for in vivo binding studies at the CB1 receptor with a higher affinity (Ki = 7.49 nM) for CB1 than the parent compound (Ki = 11.5 nM). AM-251 has been employed in competitive binding studies to identify CB1 affinity of different cannabimimetic agonists in vivo. AM-251 is also a potent activator of the GPR55 receptor. Daily injection of AM-251 in obese Zucker rats produced a marked and sustained decrease in daily food intake and body weight and a considerable increase in energy expenditure in comparison with untreated obese Zucker rats. AM-251 administration to obese rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol whereas HDL cholesterol plasma levels increased. AM-251 represents a promising therapeutic strategy for the treatment of obesity and metabolic syndrome.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cannabinoid CB1 receptor 85 Target ID: CHEMBL218 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10052983 \| https://www.ncbi.nlm.nih.gov/pubmed/19338772 \| https://www.ncbi.nlm.nih.gov/pubmed/18333607	Antagonist 2778		3.5 nM [IC50]
G-protein coupled receptor 55 6 Target ID: CHEMBL1075322 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17876302	Agonist 2678		39.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14665975 https://www.ncbi.nlm.nih.gov/pubmed/23932644 https://www.ncbi.nlm.nih.gov/pubmed/23033907 https://www.ncbi.nlm.nih.gov/pubmed/21395869	Primary		Preclinical	Unknown Approved Use Unknown
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25188001 https://www.ncbi.nlm.nih.gov/pubmed/21645531 http://www.coalition4paintreatment.com/1/26/552/intrathecal-palmitoylethanolamide-and-am251-and-spinal-cord-il1-beta-expression-details	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
		20627362
Inhibition of methamphetamine self-administration in rats by cannabinoid receptor antagonist AM 251.	2002 Jun	12095072
Differences in the relative potency of SR 141716A and AM 251 as antagonists of various in vivo effects of cannabinoid agonists in C57BL/6J mice.	2007 Aug 13	17553486
Involvement of cannabinoid (CB1)-receptors in the development and maintenance of opioid tolerance.	2007 May 25	17395382
Calcium release from presynaptic internal stores is required for ethanol to increase spontaneous gamma-aminobutyric acid release onto cerebellum Purkinje neurons.	2007 Oct	17652632
Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats.	2007 Sep	17634345
The effects of cannabidiol and tetrahydrocannabinol on motion-induced emesis in Suncus murinus.	2008 Aug	18816298
CB1-cannabinoid receptors are involved in the modulation of non-synaptic [3H]serotonin release from the rat hippocampus.	2008 Jan	17719142
Glutamate spillover modulates GABAergic synaptic transmission in the rat midbrain periaqueductal grey via metabotropic glutamate receptors and endocannabinoid signaling.	2008 Jan 23	18216189
Cannabinoids and hamster circadian activity rhythms.	2008 Jul 30	18582849
Constitutive activity at the cannabinoid CB1 receptor is required for behavioral response to noxious chemical stimulation of TRPV1: antinociceptive actions of CB1 inverse agonists.	2008 Nov 5	18987195
D2 receptor-mediated inhibition of dopamine release in the rat striatum in vitro is modulated by CB1 receptors: studies using fast cyclic voltammetry.	2009 Feb	19187091
The endocannabinoid anandamide inhibits kinin B1 receptor sensitization through cannabinoid CB1 receptor stimulation in human umbilical vein.	2009 Jan 5	19022239
Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma.	2009 Jul	19509271
Novel mGluR- and CB1R-independent suppression of GABA release caused by a contaminant of the group I metabotropic glutamate receptor agonist, DHPG.	2009 Jul 1	19568435
Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine.	2009 Mar 10	19284549
Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids.	2010 Aug	20626112
Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids.	2010 Jun	20590570
Epidermal growth factor receptor transactivation by the cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 (TRPV1) induces differential responses in corneal epithelial cells.	2010 Sep	20619260
Cytotoxicity of synthetic cannabinoids found in "Spice" products: the role of cannabinoid receptors and the caspase cascade in the NG 108-15 cell line.	2011 Nov 10	21907772
Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1.	2012 Apr	22198381
∆(9)-Tetrahydrocannabinol decreases NOP receptor density and mRNA levels in human SH-SY5Y cells.	2012 Feb	21603976
The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.	2015 Aug 6	26070387

Patents

Sample Use Guides

In Vivo Use Guide

Rats: chronic treatment with AM-251 (3 mg/kg for 3 weeks) in obese and lean Zucker rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol.

Route of Administration: Intraperitoneal

In Vitro Use Guide

The application of AM-251 (10 uM) activated a robust Ca2+ accumulation in a subset (≈35–40%) of TG neurons. The AM-251-evoked Ca2+ influxes into murine trigeminal ganglia (TG) sensory neurons were concentration-dependent. The EC50 for AM-251 was 7.37 uM. A wide range of concentrations (0.1–50 uM) of AM-251 is able to generate currents in TG sensory neurons. The activation threshold for IAM-251 was 0.1 uM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:11:43 UTC 2023` Edited by `admin` on `Sat Dec 16 08:11:43 UTC 2023`
Record UNII	3I4FA44MAI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AM-251

Common Name

English

1-(2,4-DICHLOROPHENYL)-5-(4-IODOPHENYL)-4-METHYL-N-PIPERIDIN-1-YLPYRAZOLE-3-CARBOXAMIDE

Systematic Name

English

AM251

Common Name

English

1-(2,4-DICHLOROPHENYL)-5-(4-IODOPHENYL)-4-METHYL-N-(1-PIPERIDYL)PYRAZOLE-3-CARBOXAMIDE

Systematic Name

English

Code System Code Type Description

WIKIPEDIA

AM251