Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H21Cl3N4O |
Molecular Weight | 463.787 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(Cl)C=C(Cl)C=C3)C4=CC=C(Cl)C=C4
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)
DescriptionSources: https://www.drugbank.ca/drugs/DB06155Curator'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
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trade names Acomplia, Zimulti) was an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects.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 |
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Target ID: CHEMBL218 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21334892 |
11.22 nM [IC50] | ||
Target ID: CHEMBL253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18712856 |
1939.8 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Zimulti Approved UseUnknown |
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Primary | Zimulti Approved UseUnknown |
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Primary | Zimulti Approved UseUnknown |
PubMed
Title | Date | PubMed |
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Cannabinoid CB(1) receptors colocalize with tyrosine hydroxylase in cultured fetal mesencephalic neurons and their activation increases the levels of this enzyme. | 2000 Feb 28 |
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Cannabinoid-mediated inhibition of inducible nitric oxide production by rat microglial cells: evidence for CB1 receptor participation. | 2001 |
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Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. | 2001 |
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Reduction of opioid dependence by the CB(1) antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction. | 2001 Apr |
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Effect of vanilloid drugs on gastrointestinal transit in mice. | 2001 Apr |
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The activity of anandamide at vanilloid VR1 receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism. | 2001 Apr 20 |
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CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum. | 2001 Jan |
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Synergistic efects of opioid and cannabinoid antagonists on food intake. | 2001 Jan 1 |
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Effects of cannabinoids on prefrontal neuronal responses to ventral tegmental area stimulation. | 2001 Jul |
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Identification of two distinct vasodilator pathways activated by ATP in the mesenteric bed of the rat. | 2001 Jul |
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Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. | 2001 Jul |
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Functional interaction between opioid and cannabinoid receptors in drug self-administration. | 2001 Jul 15 |
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Anandamide-induced sleep is blocked by SR141716A, a CB1 receptor antagonist and by U73122, a phospholipase C inhibitor. | 2001 Jul 20 |
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The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain. | 2001 Jun |
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Endogenous cannabinoid anandamide increases heart resistance to arrhythmogenic effects of epinephrine: role of CB(1) and CB(2) receptors. | 2001 Mar |
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2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizing factor. | 2001 Mar |
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Pharmacological analysis of cannabinoid receptor activity in the rat vas deferens. | 2001 Mar |
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Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. | 2001 Mar 29 |
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Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. | 2001 May 1 |
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Effects of cannabinoids on adrenaline release from adrenal medullary cells. | 2001 Nov |
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Rapid tolerance to Delta(9)-tetrahydrocannabinol and cross-tolerance between ethanol and Delta(9)-tetrahydrocannabinol in mice. | 2001 Nov 16 |
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The cannabinoid receptor antagonist SR 141716 prevents acquisition of drinking behavior in alcohol-preferring rats. | 2001 Nov 2 |
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Cannabinoid CB(1) receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues. | 2001 Nov 23 |
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Interaction of anandamide with the M(1) and M(4) muscarinic acetylcholine receptors. | 2001 Oct 5 |
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Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic ethanol administration. | 2001 Sep |
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Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters. | 2001 Sep |
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Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and peripheral mechanisms. | 2001 Sep |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28315677
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.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C28197
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EMA ASSESSMENT REPORTS |
ZIMULTI (WITHDRAWN: OBESITY)
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EMA ASSESSMENT REPORTS |
ACOMPLIA (WITHDRAWN: OBESITY)
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WHO-VATC |
QA08AX01
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WHO-ATC |
A08AX01
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8029
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C089032
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RIMONABANT
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SUB21719
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RR-26
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100000089586
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34967
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DB06155
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m9625
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743
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C73244
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RML78EN3XE
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CHEMBL111
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DTXSID3046453
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168273-06-1
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104850
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4150
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE TOXIC (PARENT)
SALT/SOLVATE (PARENT)