Will the new CB1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?

  title={Will the new CB1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?},
  author={Sheila Anne Doggrell},
  journal={Expert Opinion on Investigational Drugs},
  pages={339 - 342}
  • S. Doggrell
  • Published 1 March 2005
  • Medicine
  • Expert Opinion on Investigational Drugs
Obesity and alcoholism are two common modern-day diseases. The cannabinoid CB1 receptor antagonist rimonabant is in Phase III clinical trial for the treatment of obesity with preliminary results showing that it decreases appetite and body weight. Animal studies have shown that rimonabant is effective in the treatment of alcoholism. SR-147778 is a new potent and selective CB1 receptor antagonist. In animals, SR-147778 has been shown to inhibit CB1 receptor-mediated hypothermia, analgesia and… 
Cannabinoid CB1 receptor antagonists in therapeutic and structural perspectives.
Rimonabant showed clinical efficacy in the treatment of obesity and also improved cardiovascular and metabolic risk factors, and its poor pharmacokinetic properties were successfully optimized which led to the discovery of orally active and highly CB1/CB2 receptor selective analogs in this series.
Efficacy of a dose range of surinabant, a cannabinoid receptor blocker, for smoking cessation: a randomized controlled clinical trial
Surinabant did not improve smoking cessation rates compared with placebo, but had a small effect on reducing post-cessation weight gain.
Investigational therapies in the treatment of obesity
Investigational antiobesity medications can modulate energy homeostasis by stimulating catabolic or inhibiting anabolic pathways, but differing approaches are reviewed and commented on.
Synthesis and Pharmacological Evaluation of Analogs of Indole‐Based Cannabimimetic Agents
To investigate the structure–activity relationships (SAR) for the binding of non‐classical agonists to CB1 and CB2 cannabinoid receptors, a series of indole derivatives were designed and synthesized.
Noladin ether, a putative endocannabinoid, enhances motivation to eat after acute systemic administration in rats
This study examined the acute actions of the putative endocannabinoid noladin ether on food intake and eating motivation, assessing how it affects the amount of work expended by animals to obtain food.
Prediction of the binding affinities and selectivity for CB1 and CB2 ligands using homology modeling, molecular docking, molecular dynamics simulations, and MM-PBSA binding free energy calculations.
Comparisons of binding free energies, ligand-receptor interaction patterns and hotspot residues among the four systems, namely, agonist-bound CB1, agonists and antagonists of both CB1 and CB2, enabled to investigate and identify distinct binding features of these four systems with which one can rationally design potent, selective and function-specific modulators for the cannabinoid receptors.


Suppressing effect of the cannabinoid CB1 receptor antagonist, SR147778, on alcohol intake and motivational properties of alcohol in alcohol-preferring sP rats.
The results extend to SR147778 the anti-alcohol profile of the prototype cannabinoid CB(1) receptor antagonist, rimonabant (SR141716), and strengthen the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol.
Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors
These results suggest for the first time that endogenous cannabinoid systems may modulate the appetitive value of sucrose and ethanol, perhaps by affecting the activity of brain reward systems.
SR141716A, a potent and selective antagonist of the brain cannabinoid receptor
SR147778 [5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide], a New Potent and Selective Antagonist of the CB1 Cannabinoid Receptor: Biochemical and Pharmacological Characterization
SR147778 (0.3–3 mg/kg) is shown to antagonize pharmacological effects (hypothermia, analgesia, and gastrointestinal transit) induced by R-(+)-(2,3-dihydro-5-methyl-3-[{4-morpholinyl}methyl] pyrol [1,2,4-benzoxazin-6-yl)(1-naphthalenyl) methanone in mice.
Pharmacotherapy of alcohol dependence: a review of the clinical data.
  • K. Mann
  • Medicine, Psychology
    CNS drugs
  • 2004
Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone.
Obesity in Adulthood and Its Consequences for Life Expectancy: A Life-Table Analysis
An estimate of the effect of obesity and overweight in adulthood on life expectancy is provided, implicitly taking into account the various possible weight trajectories throughout the life course, based on data from the Framingham Heart Study.
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