Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis

  title={Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis},
  author={David R Janero and Alexandros Makriyannis},
  journal={Expert Opinion on Emerging Drugs},
  pages={43 - 65}
The endogenous cannabinoid (CB) (endocannabinoid) signaling system is involved in a variety of (patho)physiological processes, primarily by virtue of natural, arachidonic acid-derived lipids (endocannabinoids) that activate G protein-coupled CB1 and CB2 receptors. A hyperactive endocannabinoid system appears to contribute to the etiology of several disease states that constitute significant global threats to human health. Consequently, mounting interest surrounds the design and profiling of… 

Peripherally restricted CB1 receptor blockers.

Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products

It is expected that more novel cannabinoids will be discovered and forecasted as promising drug leads from diverse natural sources and species, such as animal venoms which constitute a true pharmacopeia of toxins modulating diverse targets, with astonishing affinity and selectivity.

A patent update on cannabinoid receptor 1 antagonists (2015-2018)

Taking together, peripherally acting CB1 receptor antagonists and modulators are an emerging class of drugs for metabolic syndrome, non-alcoholic steatohepatitis (NASH) and other important disorders where this receptor has been implicated.

The Molecular Basis of Cannabinoid Activity: Application to Therapeutics Design and Discovery for Cannabis Use Disorders

Intrinsic pharmacological properties of CB1R neutral antagonists and MGL and FAAH inhibitors are regarded as key to potentially safe and efficacious medications for treating acute cannabis toxicity and/or CUDs.

Translational potential of allosteric modulators targeting the cannabinoid CB1 receptor

This paper reviews and summarizes the complex pharmacological profiles of each class of CB1 allosteric modulators, the development of new classes of CB 1 allosterics modulators and the results from in vivo assessments of their therapeutic value.

Cannabinoid CB1 receptor‐interacting proteins: novel targets for central nervous system drug discovery?

This review examines CB1 receptor‐interacting proteins, including heterotrimeric G‐proteins, but with particular emphasis on non‐G‐protein entities, that might comprise the CB1 receptosomal complex.

Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522 with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice

The in vivo pharmacodynamic study revealed that TXX-522 had good oral bioavailability and a potent anti-obesity effect, and ameliorated insulin resistance in high-fat diet-induced obese mice, and showed minimal brain penetration.

Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives

Pre-clinical findings show that CBG reduces intraocular pressure, possesses antioxidant, anti-inflammatory, and anti-tumoral activities, and has anti-anxiety, neuroprotective, dermatological, and appetite-stimulating effects, suggesting that research on CBG deserves to be deepened.

Cannabinoid 1 G protein-coupled receptor (periphero-)neutral antagonists: emerging therapeutics for treating obesity-driven metabolic disease and reducing cardiovascular risk

CB1R (periphero-)neutral antagonists merit continued analysis of their molecular pharmacology and evaluation of their therapeutic significance and translational potential as new-generation medicines for obesity-related derangements, including nonalcoholic fatty liver disease and type 2 diabetes, if not obesity itself.



The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism – or inverse agonism – as potential obesity treatment and other therapeutic use

The basic science of the endocannabinoid system and the therapeutic potential of cannabinoid receptor antagonists are summarized, with emphasis on the treatment of obesity.

Targeted modulators of the endogenous cannabinoid system: Future medications to treat addiction disorders and obesity

The rational design of targeted CB1 cannabinoid-receptor modulators are a promising route to future medications with significant therapeutic impact against psychobehavioral and metabolic disturbances having a reward-supported appetitive component.

A critical review of the cannabinoid receptor as a drug target for obesity management

How close cannabinoid receptor antagonists are to the ideal anti‐obesity drug, with respect to their mechanisms of action, clinical effectiveness and safety is discussed.

Blocking the Cannabinoid Receptors: Drug Candidates and Therapeutic Promises

  • G. Muccioli
  • Biology, Medicine
    Chemistry & biodiversity
  • 2007
The pharmacological tools that are currently available and the animal studies supporting the therapeutic use of cannabinoid receptor antagonists and inverse agonists are described.

Modulation of the endocannabinoid system in cardiovascular disease: therapeutic potential and limitations.

In the absence of a cellular storage mechanism for endocannabinoids, their tissue levels are determined by the balance between the rate of their “on-demand” synthesis and their enzymatic degradation.

CB1 cannabinoid antagonists: structure-activity relationships and potential therapeutic applications.

The current review will mainly focus on the structure-activity relationships that have been established for antagonists/inverse agonists that bind to the CB1 cannabinoid receptors and on their therapeutic applications.

Should peripheral CB(1) cannabinoid receptors be selectively targeted for therapeutic gain?

Cannabinoid receptors as therapeutic targets.

An overview of structural aspects governing cannabinoid receptor function, the cannabinergic system and its physiological functions is presented and it is clear that it is possible to produce ligands that result in differential responses.

Rimonabant: a novel selective cannabinoid-1 receptor antagonist for treatment of obesity.

  • P. PatelRolee Pathak
  • Medicine, Biology
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2007
Rimonabant, a selective CB(1) antagonist, is a novel treatment option for obese and overweight individuals and significant weight loss, decrease in waist circumference, and improvements in lipid profile and glucose control have been shown in clinical trials of rimonabant.