"目录号: HY-14137
GPCR/G ProteinAutophagy-
Rimonabant hydrochloride 是一种大麻素受体 (cannabinoid receptor) 拮抗剂，高亲和力地选择性结合到中枢大麻素受体 (CB1)，Ki为 2 nM。
Cannabinoid ReceptorAutophagy
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生物活性
Description
Rimonabant hydrochloride is acannabinoid receptorantagonist, which binds selectively to central cannabinoid receptors (CB1) with high affinity (Ki=2 nM).
IC50& Target
Ki: 2 nM (CB1 receptor)[1]
In Vitro
Rimonabant hydrochloride (SR 141716A) binds selectively to central cannabinoid receptors (CB1) with high affinity (Ki=2 nM), and blocks the inhibitory effects of cannabinoid receptor agonists in the mouse vas deferens, dopamine-stimulated adenylyl cyclase and WIN 55212-stimulated GTPγS binding[1]. Rimonabant dose-dependently inhibited CO synthesis in Raw 264.7 macrophages, with 1 μM producing a significant (~40%) decrease compared to untreated controls and concentrations ≥ 5 μM producing near complete inhibition. A small, but significant, reduction of TG and DG synthesis is also observed with Rimonabant at concentrations ≥ 10 μM. Inhibition of CO synthesis in Raw 264.7 macrophages by Rimonabant (IC50value 2.9±0.38 μM) is very similar to that of AM251 and SR144528 (IC50value 2.6±0.26 μM and 2.5±0.32 μM, respectively), two related compounds previously demonstrated to be potent ACAT inhibitors. Mouse peritoneal macrophages also displayed significantly reduced CO synthesis in response to Rimonabant treatment. Rimonabant at concentrations ≥ 1 μM significantly inhibits CO synthesis in CHO-ACAT1 and CHO-ACAT2 cells in a concentration-dependent manner with similar efficiency (IC50s of 1.5±1.2 μM and 2.2±1.1 μM, respectively)[2].
In Vivo
Pretreatment with Rimonabant hydrochloride (SR 141716A) blocks the antinociceptive, discriminative stimulus, memory impairing and hypolocomotor effects produced by Δ-9-THC. SR 141716A also precipitates a withdrawal syndrome in rats treated chronically with Δ-9-THC[1]. Pretreatment of mice with 0.1?mg/kg of WIN 55212-2 is effective in increasing the CPP induced by MDMA , while 1?mg/kg of Rimonabant specifically blocks CB1 receptors and does not act as an inverse agonist[3].
Clinical Trial
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Carotid Artery Plaque-Arteriosclerosis-Obesity-Metabolic Syndrome X
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Diabetes Mellitus, Type 2
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Obesity-Diabetes Mellitus Type 2
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Diabetes Mellitus, Type 2
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Smoking Cessation
November 2002
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Diabetes Mellitus, Type 2
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Smoking Cessation
September 2002
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Obesity-Microalbuminuria-Diabetes Mellitus, Type 2-Dyslipidemia
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Maintenance of Smoking Cessation
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Healthy-Alcohol Drinking
December 31, 2003
Phase 2
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Obesity-Eating Disorders
August 2004
Phase 3
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Sanofi
Obesity-Weight Loss
April 2008
Phase 3
NCT00459004
Sanofi
Obesity
October 2004
Phase 2
NCT00458718
Sanofi
Smoking Cessation
September 2004
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University Hospital, Clermont-Ferrand
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September 2008
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Dyslipidemia-Obesity
May 2005
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Obesity
May 2004
Phase 3
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Obesity
October 2001
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Coronary Atherosclerosis
January 2005
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NCT00408148
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Obesity
October 2006
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NCT00257257
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Type 2 Diabetes Mellitus
March 2005
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Obesity
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Type 2 Diabetes Mellitus
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National Institute on Drug Abuse (NIDA)-National Institutes of Health Clinical Center (CC)
Cannabis-Dependence
April 16, 2006
Phase 1
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The Scripps Research Institute-National Institute on Drug Abuse (NIDA)
Cannabis Dependence-Cannabis Withdrawal
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Phase 2
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Obesity-Weight Loss
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Obesity-Diabetes Mellitus, Non-Insulin-Dependent-Obesity in Diabetes
October 2001
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Obesity-Dyslipidemia
September 2001
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Hospital Arnau de Vilanova-Pfizer
Atherosclerosis-Cardiovascular Diseases
April 2008
Phase 4
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Aristotle University Of Thessaloniki
Carotid Atherosclerosis-Stroke-Type 2 Diabetes-Metabolic Syndrome
September 2005
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References
[1].Vivian JA, et al. Analgesic, respiratory and heart rate effects of cannabinoid and opioid agonists in rhesus monkeys: antagonist effects of SR 141716A. J Pharmacol Exp Ther. 1998 Aug;286(2):697-703.
[2].Netherland C, et al. Rimonabant is a dual inhibitor of acyl CoA:cholesterol acyltransferases 1 and 2. Biochem Biophys Res Commun. 2010 Aug 6;398(4):671-6.
[3].Rodríguez-Arias M, et al. Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait. Neural Plast. 2016;2016:6481862.