Abstract
The advent of the highly selective cannabinoid receptor (CB1) antagonist, rimonabant (SR141716; Acomplia) can revolutionize the ability of the clinicians to manage obesity. Large-scale clinical trials have demonstrated that rimonabant therapy can reduce obesity. Although, the precise mechanisms of action of rimonabant have to be further dissected, it is emerging, from both preclinical and clinical research, that not only is rimonabant an antiobesity drug, but also its pleiotropic functions affect a broad range of diseases, from obesity-related comorbidities to drug dependence and cancer. Here we review recent data from the literature and discuss the full pharmacological potential of this drug.
Footnotes
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We thank the Associazione Educazione e Ricerca Medica Salernitana (ERMES) for supporting our studies. A.S. was supported by a fellowship from Associazione Italiana Ricerca sul Cancro.
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
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doi:10.1124/mol.106.033118.
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ABBREVIATIONS: THC, Δ9-tetrahydrocannabinol; AEA, anandamide (N-arachidonoylethanolamine); SR141716, N-(piperidino-1-yl)-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-pyrazole-3-carboxamide; CP 55,940, (1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol; WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone; MAPK, mitogen-activated protein kinase; HDL, high-density lipoprotein; RIO, rimonabant in obesity; DA, dopamine; msP, Marchigian Sardinian alcohol preferring rats; SR144528, N-((1S)-endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide); LPS, lipopolysaccharide; TNF, tumor necrosis factor; MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-{[5(trifluoromethyl)pyridin-2-yl]oxy}propanamide; SR147778, [5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide].
- Received November 29, 2006.
- Accepted February 27, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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