The Nonpsychotropic Cannabinoid Cannabidiol Modulates and Directly Activates Alpha-1 and Alpha-1-Beta Glycine Receptor Function

@article{Ahrens2009TheNC,
  title={The Nonpsychotropic Cannabinoid Cannabidiol Modulates and Directly Activates Alpha-1 and Alpha-1-Beta Glycine Receptor Function},
  author={J{\"o}rg Ahrens and Reyhan Demir and Martin Leuwer and Jeanne de la Roche and Klaus Krampfl and Nilufar Foadi and Matthias Karst and Gertrud Haeseler},
  journal={Pharmacology},
  year={2009},
  volume={83},
  pages={217 - 222}
}
Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of chronic pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. Cannabidiol is a nonpsychotropic plant constituent of Cannabis sativa. As we hypothesized that non-CB receptor mechanisms of cannabidiol might contribute to its anti-inflammatory and neuroprotective effects, we investigated the… 

Figures from this paper

Nonpsychoactive Cannabinoid Action on 5-HT3 and Glycine Receptors

This chapter summarizes recent research progress in knowledge about the mechanisms and in vivo consequence of cannabinoid modulation of 5-HT3 and glycine receptors to help develop novel therapeutic agents for the treatment of pain and other diseases.

Lack of positive allosteric modulation of mutated α1S267I glycine receptors by cannabinoids

This study investigated the impact of the amino acid residue serine at position 267 on the glycine-modulatory effects of ajulemic acid, cannabidiol and HU210 and found that the mutation of the α1 subunit TM2 serine residue to isoleucine abolished the co-activation and the direct activation of the glyine receptor by the investigated cannabinoids.

Therapeutic Potential of Nonpsychoactive Cannabinoids by Targeting at Glycine Receptors

Recent development in studies of mechanism and therapeutic potential of cannabinoid modu‐ lation of GlyR subunits shows considerable promise toward the development of novel therapeutic agents acting at defined modulatory sites of GlyRs in the treatment of various chronic pain, neuromotor disorders, and other GlyR deficiency diseases.

Paracetamol Fails to Positively Modulate and Directly Activate Chloride Currents in Human α1-Glycine Receptors

The analgesic actions of paracetamol leading to pain relief appear to be mediated via other mechanisms, but not via activation of spinal glycinergic pathways.

Cannabinoid potentiation of glycine receptors contributes to cannabis-induced analgesia.

Using mutagenesis and NMR analysis, a serine at 296 in the GlyR protein critical for the potentiation of I(Gly) by Δ(9)-tetrahydrocannabinol (THC), a major psychoactive component of marijuana is identified.

Modulation of Glycine Receptor-Mediated Pain Signaling in vitro and in vivo by Glucose

Glucose showed mild analgesic effects and was able to compensate for strychnine-induced allodynia in mice and suggest a molecular mechanism for glucose-mediated analgesia.

Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor

Cannabidiol displays antagonist-like activity toward σ1R to reduce the negative effects of NMDAR overactivity in the abovementioned experimental situations.

A Common Molecular Basis for Exogenous and Endogenous Cannabinoid Potentiation of Glycine Receptors

Sustained incubation with the endocannabinoid anandamide substantially increased the amplitude of glycine-activated current in both rat cultured spinal neurons and in HEK-293 cells expressing human α1, rat α2 and α3 GlyRs, suggesting that exogenous and endogenous cannabinoids potentiate GlyRs via a hydrogen bonding-like interaction.

Antinociception mechanisms of action of cannabinoid-based medicine: an overview for anesthesiologists and pain physicians

  • S. Narouze
  • Biology, Medicine
    Regional Anesthesia & Pain Medicine
  • 2020
This narrative review evaluates cannabinoids’ diverse mechanisms of action as it pertains to nociception modulation relevant to the practice of anesthesiologists and pain medicine physicians.
...

References

SHOWING 1-10 OF 26 REFERENCES

Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors

It is concluded that the contribution of CB1-type receptors expressed on the peripheral terminals of nociceptors to cannabinoid-induced analgesia is paramount, which should enable the development of peripherally acting CB1 analgesic agonists without any central side effects.

Δ9-Tetrahydrocannabinol and Endogenous Cannabinoid Anandamide Directly Potentiate the Function of Glycine Receptors

The results indicate that THC and AEA, in pharmacologically relevant concentrations, directly potentiate the function of GlyRs through an allosteric mechanism.

The glycinergic control of spinal pain processing

  • H. Zeilhofer
  • Biology
    Cellular and Molecular Life Sciences CMLS
  • 2005
The central component of inflammatory pain originates from a disinhibition of dorsal horn neurons, which are relieved from glycinergic neurotransmission by the inflammatory mediator prostaglandin E2 (PGE2).

[The synthetic cannabinoid analog WIN 55,212-2 potentiates the amplitudes of glycine-activated currents].

The data allow us to suggest the existence of a CB1R independent action of cannabinoids directly on glycine-activated currents, representing a novel antinociceptive mechanism of this compounds.

Reversal of pathological pain through specific spinal GABAA receptor subtypes

It is shown that their selective activation by the non-sedative (‘α1-sparing’) benzodiazepine-site ligand L-838,417 is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development.

The interaction of anaesthetic steroids with recombinant glycine and GABAA receptors.

Comparing the EC50 values reported here with free plasma concentrations during steroid-induced anaesthesia indicates that a selective modulation of GABAA receptor activity is likely to occur in vivo.

On the pharmacological properties of Delta9-tetrahydrocannabinol (THC).

  • B. Costa
  • Biology
    Chemistry & biodiversity
  • 2007
Emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis-based medicines as new perspective to revisit the pharmacology of this plant.

Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors

Observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetic action.

On the Pharmacological Properties of Δ9‐Tetrahydrocannabinol (THC)

Emerging evidence highlights the beneficial effects of the whole cannabis extract over those observed with single components, indicating cannabis‐based medicines as new perspective to revisit the pharmacology of this plant.