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 2849		3.5 nM [IC50]
G-protein coupled receptor 55 6 Target ID: CHEMBL1075322 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17876302	Agonist 2752		39.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 206 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 619 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
The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.	2015-08-06	26070387
The cannabinoid receptor antagonist AM251 increases paraoxon and chlorpyrifos oxon toxicity in rats.	2015-01	25447325
Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death.	2014-01-01	24211273
Comparative effects of parathion and chlorpyrifos on extracellular endocannabinoid levels in rat hippocampus: influence on cholinergic toxicity.	2013-11-01	23933531
Hepatic cannabinoid receptor type 1 mediates alcohol-induced regulation of bile acid enzyme genes expression via CREBH.	2013	23894352
Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1.	2012-04	22198381
Δ(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells.	2012-04	21595653
∆(9)-Tetrahydrocannabinol decreases NOP receptor density and mRNA levels in human SH-SY5Y cells.	2012-02	21603976
Cytotoxicity of synthetic cannabinoids found in "Spice" products: the role of cannabinoid receptors and the caspase cascade in the NG 108-15 cell line.	2011-11-10	21907772
Interactions between endocannabinoid and serotonergic systems in mood disorders caused by nicotine withdrawal.	2011-04	21324836
Retrograde release of endocannabinoids inhibits presynaptic GABA release to second-order baroreceptive neurons in NTS.	2010-12-08	20580326
The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats.	2010-12-02	20888328
Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice.	2010-09-01	20571060
Epidermal growth factor receptor transactivation by the cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 (TRPV1) induces differential responses in corneal epithelial cells.	2010-09	20619260
Mechanisms of TNFalpha-induced cardiac dysfunction in cholestatic bile duct-ligated mice: interaction between TNFalpha and endocannabinoids.	2010-08	20626112
Effects of COX-2 inhibition on spinal nociception: the role of endocannabinoids.	2010-06	20590570
Evidence for both inverse agonism at the cannabinoid CB1 receptor and the lack of an endogenous cannabinoid tone in the rat and guinea-pig isolated ileum myenteric plexus-longitudinal muscle preparation.	2010-06	20590566
GPR55 ligands promote receptor coupling to multiple signalling pathways.	2010-06	20136841
Endocannabinoid regulation of spinal nociceptive processing in a model of neuropathic pain.	2010-04	20384778
Signaling pathways from cannabinoid receptor-1 activation to inhibition of N-methyl-D-aspartic acid mediated calcium influx and neurotoxicity in dorsal root ganglion neurons.	2009-12	19752241
Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands.	2009-10-23	19723626
Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.	2009-09-22	19595742
Characterization of anandamide-stimulated cannabinoid receptor signaling in human ULTR myometrial smooth muscle cells.	2009-09	19477951
Endogenous cannabinoids induce fever through the activation of CB1 receptors.	2009-08	19681872
Novel mGluR- and CB1R-independent suppression of GABA release caused by a contaminant of the group I metabotropic glutamate receptor agonist, DHPG.	2009-07-01	19568435
Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma.	2009-07	19509271
Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents.	2009-07	19422370
Comparison between spontaneous and kainate-induced gamma oscillations in the mouse hippocampus in vitro.	2009-06	19490088
Neurochemical evidence that stimulation of CB1 cannabinoid receptors on GABAergic nerve terminals activates the dopaminergic reward system by increasing dopamine release in the rat nucleus accumbens.	2009-06	19428788
Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine.	2009-03-10	19284549
D2 receptor-mediated inhibition of dopamine release in the rat striatum in vitro is modulated by CB1 receptors: studies using fast cyclic voltammetry.	2009-02	19187091
The endocannabinoid anandamide inhibits kinin B1 receptor sensitization through cannabinoid CB1 receptor stimulation in human umbilical vein.	2009-01-05	19022239
Effect of cannabinoids upon the uptake of folic acid by BeWo cells.	2009	19145103
Constitutive activity at the cannabinoid CB1 receptor is required for behavioral response to noxious chemical stimulation of TRPV1: antinociceptive actions of CB1 inverse agonists.	2008-11-05	18987195
Cannabinoid modulation of cutaneous Adelta nociceptors during inflammation.	2008-11	18784270
Methanandamide allosterically inhibits in vivo the function of peripheral nicotinic acetylcholine receptors containing the alpha 7-subunit.	2008-09	18567834
The effects of cannabidiol and tetrahydrocannabinol on motion-induced emesis in Suncus murinus.	2008-08	18816298
Cannabinoids and hamster circadian activity rhythms.	2008-07-30	18582849
Opposite action of hippocampal CB1 receptors in memory reconsolidation and extinction.	2008-07-17	18554811
Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre-clinical and clinical studies.	2008-06	18482433
Analysis of promoter regions regulating basal and interleukin-4-inducible expression of the human CB1 receptor gene in T lymphocytes.	2008-03	18156315
Glutamate spillover modulates GABAergic synaptic transmission in the rat midbrain periaqueductal grey via metabotropic glutamate receptors and endocannabinoid signaling.	2008-01-23	18216189
Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1.	2008-01-02	18159069
CB1-cannabinoid receptors are involved in the modulation of non-synaptic [3H]serotonin release from the rat hippocampus.	2008-01	17719142
Functional blockage of the cannabinoid receptor type 1 evokes a kappa-opiate-dependent analgesia.	2007-12	17953671
The orphan receptor GPR55 is a novel cannabinoid receptor.	2007-12	17876302
The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells.	2007-11-15	17583570
Calcium release from presynaptic internal stores is required for ethanol to increase spontaneous gamma-aminobutyric acid release onto cerebellum Purkinje neurons.	2007-10	17652632
Differential sensitivity of GABA A receptor-mediated IPSCs to cannabinoids in hippocampal slices from adolescent and adult rats.	2007-09	17634345
Role of cannabinoid type 1 receptors in locomotor activity and striatal signaling in response to psychostimulants.	2007-06-27	17596442

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 `Mon Mar 31 21:55:54 GMT 2025` Edited by `admin` on `Mon Mar 31 21:55:54 GMT 2025`
Record UNII	3I4FA44MAI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AM-251

Common Name

English

AM251

Preferred Name

English

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

Systematic 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