RIMONABANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H21Cl3N4O
Molecular Weight	463.788
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1c(C(=NN2CCCCC2)O)nn(-c3ccc(cc3Cl)Cl)c1-c4ccc(cc4)Cl

InChI

InChIKey=JZCPYUJPEARBJL-UHFFFAOYSA-N

InChI=1S/C22H21Cl3N4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-9-17(24)13-18(19)25)21(14)15-5-7-16(23)8-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)

HIDE SMILES / InChI

Molecular Formula	C22H21Cl3N4O
Molecular Weight	463.788
Charge	0
Count

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

Description
Sources: https://www.drugbank.ca/drugs/DB06155
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21334892 | https://www.ncbi.nlm.nih.gov/pubmed/18712856 | https://www.ncbi.nlm.nih.gov/pubmed/21951309 | https://clinicaltrials.gov/ct2/show/record/NCT00228176 | https://clinicaltrials.gov/ct2/show/NCT00584389 | https://clinicaltrials.gov/ct2/show/NCT00576667 | https://www.ncbi.nlm.nih.gov/pubmed/7776817 | https://www.ncbi.nlm.nih.gov/pubmed/28315677

Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) was an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects. Rimonabant is an inverse agonist for the cannabinoid receptor CB1 and was the first drug approved in that class. There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviors. It is, therefore, reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders. Data from clinical trials submitted to regulatory authorities showed that rimonabant caused depressive disorders or mood alterations in up to 10% of subjects and suicidal ideation in around 1%, and in Europe, it was contraindicated for people with any psychiatric disorder, including depressed or suicidal people. Additionally, nausea and upper respiratory tract infections were very common (occurring in more than 10% of people) adverse effects; common adverse effects (occurring in between 1% and 10% of people) included gastroenteritis, anxiety, irritability, insomnia and other sleep disorders, hot flushes, diarrhea, vomiting, dry or itchy skin, tendonitis, muscle cramps and spasms, fatigue, flu-like symptoms, and increased risk of falling.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cannabinoid CB1 receptor 81 Target ID: CHEMBL218 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21334892	Inverse Agonist 72		11.22 nM [IC50]
Cannabinoid CB2 receptor 68 Target ID: CHEMBL253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18712856	Inverse Agonist 72		1939.8 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Obesity 194 Sources: https://clinicaltrials.gov/ct2/show/NCT00584389	Primary	Approved 8043	Zimulti Approved Use Unknown
Fatty liver disease 10 Sources: https://clinicaltrials.gov/ct2/show/NCT00576667	Primary	Phase III 643	Zimulti Approved Use Unknown
Arteriosclerosis 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00228176	Primary	Phase III 643	Zimulti Approved Use Unknown

PubMed

Title	Date	PubMed
Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation.	2001	11727767
Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus.	2001	11564411
Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system.	2001	11457579
Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats.	2001 Aug	11498718
(R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide.	2001 Aug	11498713
The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in rat cerebral cortex: an in vivo and in vitro study.	2001 Aug	11459762
Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor.	2001 Aug 1	11479216
Modulation of cytokine responses in Corynebacterium parvum-primed endotoxemic mice by centrally administered cannabinoid ligands.	2001 Aug 3	11672577
The cannabinoid CB(1) receptor antagonist SR141716A increases norepinephrine outflow in the rat anterior hypothalamus.	2001 Aug 31	11527547
Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity.	2001 Aug 31	11514075
Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors.	2001 Dec	11714882
Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth.	2001 Dec	11687506
Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission.	2001 Jul	11553284
Effects of cannabinoids on prefrontal neuronal responses to ventral tegmental area stimulation.	2001 Jul	11488953
Identification of two distinct vasodilator pathways activated by ATP in the mesenteric bed of the rat.	2001 Jul	11454655
Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis.	2001 Jul	11433348
Mechanisms of endocannabinoid inactivation: biochemistry and pharmacology.	2001 Jul	11408519
Functional interaction between opioid and cannabinoid receptors in drug self-administration.	2001 Jul 15	11438610
Comparative characterization in the rat of the interaction between cannabinoids and opiates for their immunosuppressive and analgesic effects.	2001 Jul 2	11431011
CB1 receptor mediated analgesia from the Nucleus Reticularis Gigantocellularis pars alpha is activated in an animal model of neuropathic pain.	2001 Jul 20	11457432
Anandamide-induced sleep is blocked by SR141716A, a CB1 receptor antagonist and by U73122, a phospholipase C inhibitor.	2001 Jul 20	11447321
Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors.	2001 Jul 6	11448486
Endogenously produced cannabinoids and liver cirrhosis.	2001 Jul 7	11454385
Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates.	2001 Jun	11465637
Cannabinoids and pain.	2001 Mar	11575713
Endogenous cannabinoid anandamide increases heart resistance to arrhythmogenic effects of epinephrine: role of CB(1) and CB(2) receptors.	2001 Mar	11427912
Critical role of the endogenous cannabinoid system in mouse pup suckling and growth.	2001 May 11	11426843
Delta9-tetrahydrocannabinol enhances cortical and hippocampal acetylcholine release in vivo: a microdialysis study.	2001 May 11	11426837
[Antiarrhythmic properties of a cannabinoid (CB) receptor agonist].	2001 May-Jun	11558437
Cannabinoid-induced motor incoordination through the cerebellar CB(1) receptor in mice.	2001 May-Jun	11420093
Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.	2001 May-Jun	11420092
Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels.	2001 Nov	11682448
Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice.	2001 Nov	11682441
Rapid tolerance to Delta(9)-tetrahydrocannabinol and cross-tolerance between ethanol and Delta(9)-tetrahydrocannabinol in mice.	2001 Nov 16	11728426
Cannabinoid CB(1) receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues.	2001 Nov 23	11730719
Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries.	2001 Oct	11606334
A cannabinoid mechanism in relapse to cocaine seeking.	2001 Oct	11590440
Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation.	2001 Oct	11588110
Cannabinoids inhibit nitric oxide production in bone marrow derived feline macrophages.	2001 Oct	11587735
Cannabinoid receptor agonist WIN 55,212-2 inhibits rat cortical dialysate gamma-aminobutyric acid levels.	2001 Oct 15	11592127
The cannabinoid CB1 receptor antagonist SR 141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2.	2001 Oct 26	11698062
Interaction of anandamide with the M(1) and M(4) muscarinic acetylcholine receptors.	2001 Oct 5	11578621
Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic ethanol administration.	2001 Sep	11584151
Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters.	2001 Sep	11566149
Differential effects of anandamide on acetylcholine release in the guinea-pig ileum mediated via vanilloid and non-CB1 cannabinoid receptors.	2001 Sep	11522608
A possible role of lipoxygenase in the activation of vanilloid receptors by anandamide in the guinea-pig bronchus.	2001 Sep	11522594
Effects of chronic Delta(9)-tetrahydrocannabinol treatment on hippocampal extracellular acetylcholine concentration and alternation performance in the T-maze.	2001 Sep	11522331
Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and peripheral mechanisms.	2001 Sep	11514089
Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice.	2001 Sep	11504797
Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity.	2001 Sep 1	11517236

Patents

Sample Use Guides

In Vivo Use Guide

20-mg once daily

Route of Administration: Oral

In Vitro Use Guide

The 661 W cells were seeded at 3×103 cells per well in 96-well plates and then incubated for 24 h. The entire medium was then replaced with fresh medium containing 1% fetal bovine serum. Rimonabant (Cayman Chemical, Ann Arbor, MI, USA) at 1–100 nM and trolox (Wako, Osaka, Japan) at 100 nM were added and, 1 h following treatment, the cells were exposed to 2500 lx of white fluorescent light (C-FPS115D; Nikon, Tokyo, Japan) for 24 h at 37 °C. The luminance was measured using a light meter, LM-332 (As One, Osaka, Japan). Nuclear staining assays were performed after an additional 24 h of incubation.

Substance Class	Chemical Created by `admin` on `Sat Jun 26 09:57:46 UTC 2021` Edited by `admin` on `Sat Jun 26 09:57:46 UTC 2021`
Record UNII	RML78EN3XE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RIMONABANT

Official Name

English

RIMONABANT [EMA EPAR]

Common Name

English

RIMONABANT [INN]

Common Name

English

RIMONABANT [MART.]

Common Name

English

ZIMULTI

Brand Name

English

RIMONABANT [JAN]

Common Name

English

RIMONABANT [MI]

Common Name

English

SR-14171

Code

English

RIMONABANT [WHO-DD]

Common Name

English

SR-141716A

Code

English

SR-141716

Code

English

SR141716

Code

English

RIMONABANT [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C28197