Targeting cannabinoid agonists for inflammatory and neuropathic pain

@article{Cheng2007TargetingCA,
  title={Targeting cannabinoid agonists for inflammatory and neuropathic pain},
  author={Yuan Cheng and Stephen Andrew Hitchcock},
  journal={Expert Opinion on Investigational Drugs},
  year={2007},
  volume={16},
  pages={951 - 965}
}
The cannabinoid receptors CB1 and CB2 are class A G-protein-coupled receptors. It is well known that cannabinoid receptor agonists produce relief of pain in a variety of animal models by interacting with cannabinoid receptors. CB1 receptors are located centrally and peripherally, whereas CB2 receptors are expressed primarily on immune cells and tissues. A large body of preclinical data supports the hypothesis that either CB2-selective agonists or CB1 agonists acting at peripheral sites, or with… 
Selective modulation of the cannabinoid type 1 (CB1) receptor as an emerging platform for the treatment of neuropathic pain.
TLDR
An overview of the chemotypes currently under investigation for the development of novel neuropathic pain treatments targeting CB1 receptors is provided.
Analgesic and antiinflammatory effects of cannabinoid receptor agonists in a rat model of neuropathic pain
TLDR
The results emphasize the therapeutic efficacy of cannabinoid receptor agonists and their inhibitory effects on the formation of gliosis and correlates these effects with their influences on spinal cord (SC) glial activation.
Novel cannabinoid receptors
  • A J Brown
  • Biology, Medicine
    British journal of pharmacology
  • 2007
TLDR
An introduction to non‐CB1/CB2 pharmacology is presented, information on GPR55 and GPR119 currently available is summarized, and their phylogenetic origin is considered, to consider what aspects of non‐ CB1/ CB2 Pharmacology, if any, they help explain.
Discovery of agonists of cannabinoid receptor 1 with restricted central nervous system penetration aimed for treatment of gastroesophageal reflux disease.
TLDR
A moderately potent and highly lipophilic series of 2-aminobenzamides was identified through focused screening of GPCR libraries and demonstrated a dose-dependent inhibition of transient lower esophageal sphincter relaxations in a dog model.
CB1 allosteric modulators and their therapeutic potential in CNS disorders
TLDR
This review will summarize and critically analyze both the in vitro characterization and in vivo validation of CB1 allosteric modulators developed to date, with a focus on CNS therapeutic effects.
Cannabinoids and muscular pain. Effectiveness of the local administration in rat
TLDR
Evidence is provided that both, CB 1 and CB 2 receptors can contribute to muscular antinociception and, interestingly, suggest that the local administration of CB agonists could be a new and useful pharmacological strategy in the treatment of muscular pain, avoiding adverse effects induced by systemic administration.
Chromenopyrazoles: Non‐psychoactive and Selective CB1 Cannabinoid Agonists with Peripheral Antinociceptive Properties
TLDR
Modelling studies suggest that full CB1 selectivity over CB2 can be explained by the presence of a pyrazole ring in the structure, and that the antinociception induced by 13 a in the orofacial test could be mediated through peripheral mechanisms.
Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis
TLDR
Experimental and clinical evidence supports the therapeutic potential of CB1 receptor antagonists to treat overweight/obesity, obesity-related cardiometabolic disorders, and substance abuse and Laboratory data suggest that CB2 receptor antagonists might be effective immunomodulatory and, perhaps, anti-inflammatory drugs.
Hemopressin is an inverse agonist of CB1 cannabinoid receptors
TLDR
The identification of hemopressin (PVNFKFLSH) as a peptide ligand that selectively binds CB1 cannabinoid receptors is identified and it is found that it exhibits antinociceptive effects when administered by either intrathecal, intraplantar, or oral routes, underscoring hemopressingin's therapeutic potential.
Current evidence of cannabinoid‐based analgesia obtained in preclinical and human experimental settings
TLDR
Human evidence presently provides only reluctant support for a broad clinical use of cannabinoid‐based medications in pain therapy, based on preclinical and human experimental research summarized in this review.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 87 REFERENCES
Therapeutic potential of cannabinoid receptor agonists as analgesic agents
  • A. Fox, S. Bevan
  • Chemistry, Medicine
    Expert opinion on investigational drugs
  • 2005
TLDR
Clinical trials are required with novel compounds that either specifically target peripheral CB1 receptors or display high selectivity for CB2 receptors to determine whether either approach can provide the level of analgesia required to fulfil the unmet medical need left by current therapies for chronic pain.
Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models
TLDR
It is reported here that chronic pain models associated with peripheral nerve injury, but not peripheral inflammation, induce CB2 receptor expression in a highly restricted and specific manner within the lumbar spinal cord.
Cannabinoid receptors as therapeutic targets.
  • K. Mackie
  • Medicine
    Annual review of pharmacology and toxicology
  • 2006
TLDR
This review considers the components of the endocannabinoid system and discusses some of the most promising endoc cannabinoidoid-based therapies.
CB2 cannabinoid receptor agonists: pain relief without psychoactive effects?
TLDR
Cannabinoid receptor agonists significantly diminish pain responses in animal models; however, they exhibit only modest analgesic effects in humans, and show promise for the treatment of acute and chronic pain without psychoactive effects.
CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids.
  • M. Ibrahim, F. Porreca, +8 authors T. Malan
  • Chemistry, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
TLDR
Test the hypothesis that CB(2) receptor activation stimulates release from keratinocytes of the endogenous opioid beta-endorphin, which then acts at local neuronal mu-opioid receptors to inhibit nociception and indicates anatomical specificity of opioid effects.
Inhibition of Inflammatory Hyperalgesia by Activation of Peripheral CB2 Cannabinoid Receptors
TLDR
The results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.
CB2 cannabinoid receptor mediation of antinociception.
TLDR
The experiments reported here strongly suggest that AM1241 produces antinociception in vivo by activating CB2 cannabinoid receptors, and confirm the potential therapeutic relevance of CB2 cannabinoids receptors for the treatment of acute pain.
Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes.
TLDR
This review will examine promising indications of cannabinoid receptor agonists to alleviate acute and chronic pain episodes and suggest new therapeutic approaches to avoid central nervous system side effects.
Control of pain initiation by endogenous cannabinoids
TLDR
It is shown that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS, and that locally generated an andamide and PEA may mediate this effect.
Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy
TLDR
Data support the tenet that selective CB2 receptor agonists have the potential to treat pain without eliciting the centrally-mediated side effects associated with non-selective cannabinoid agonists, and highlight the utility of GW405833 for the investigation of CB2 physiology.
...
1
2
3
4
5
...