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
The cannabinoids R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210), 2-O-arachidonoylglycerylether (HU-310) and arachidonyl-2-chloroethylamide (ACEA) increase isoflurane provoked sleep duration by activation of cannabinoids 1 (CB1)-receptors in mice.	2002 Jul 5	12095655
Inhibition of methamphetamine self-administration in rats by cannabinoid receptor antagonist AM 251.	2002 Jun	12095072
Novel effect of CP55,940, a CB1/CB2 cannabinoid receptor agonist, on intracellular free Ca2+ levels in bladder cancer cells.	2002 Mar 31	12005350
Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide.	2003 Jan 15	12509806
The endocannabinoid 2-arachidonylglycerol decreases the immunological activation of Guinea pig mast cells: involvement of nitric oxide and eicosanoids.	2004 Oct	15187170
Retrograde endocannabinoid signaling in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala.	2005 Jun 29	15987949
Cannabinoid CB1 receptor antagonist AM251 inhibits cocaine-primed relapse in rats: role of glutamate in the nucleus accumbens.	2006 Aug 16	16914679
Activation of cannabinoid CB1 receptors induces glucose intolerance in rats.	2006 Feb 15	16423347
Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism.	2006 Mar 20	16500647
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
Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction.	2007 Mar	17408433
2-Arachidonylglyceryl ether and abnormal cannabidiol-induced vascular smooth muscle relaxation in rabbit pulmonary arteries via receptor-pertussis toxin sensitive G proteins-ERK1/2 signaling.	2007 Mar 22	17292352
Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis.	2007 May	17484889
Involvement of cannabinoid (CB1)-receptors in the development and maintenance of opioid tolerance.	2007 May 25	17395382
CB1 receptor activation in the basolateral amygdala produces antinociception in animal models of acute and tonic nociception.	2007 May-Jun	17439413
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
Cannabinoid modulation of cutaneous Adelta nociceptors during inflammation.	2008 Nov	18784270
Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma.	2009 Jul	19509271
Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands.	2009 Oct 23	19723626
The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats.	2010 Dec 2	20888328
GPR55 ligands promote receptor coupling to multiple signalling pathways.	2010 Jun	20136841
The cannabinoid receptor antagonist AM251 increases paraoxon and chlorpyrifos oxon toxicity in rats.	2015 Jan	25447325

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 GMT 2023` Edited by `admin` on `Sat Dec 16 08:11:43 GMT 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