ReferenceID 4831
Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
Br J Pharmacol
Background and purpose: Cannabigerol (CBG), a non-psychotropic phytocannabinoid and a precursor of ∆ 9 -tetrahydrocannabinol and cannabidiol, has been suggested to act as an analgesic. A previous study reported that CBG
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4831
- Evidence Id
- 21421
- Core Evidence Id
- 21421
- Source Reference Id
- 2912
- Herb2 Reference Id
- HBREF003709
- Subject Paper Key
- HBIN019565_35297036
- Pubmed Id
- 35297036
- Doi
- 10.1111/bph.15833
- Paper Title
- Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
- Paper Abstract
- Background and purpose: Cannabigerol (CBG), a non-psychotropic phytocannabinoid and a precursor of ∆ 9 -tetrahydrocannabinol and cannabidiol, has been suggested to act as an analgesic. A previous study reported that CBG (10 μM) blocks voltage-gated sodium (Na v ) currents in CNS neurons, although the underlying mechanism is not well understood. Genetic and functional studies have validated Na v 1.7 channels as an opportune target for analgesic drug development. The effects of CBG on Na v 1.7 channels, which may contribute to its analgesic properties, have not been previously investigated. Experimental approach: To determine the effects of CBG on Na v channels, we used stably transfected HEK cells and primary dorsal root ganglion (DRG) neurons to characterize compound effects using experimental and computational techniques. These included patch-clamp, multielectrode array, and action potential modelling. Key results: CBG is a ~10-fold state-dependent Na v channel inhibitor (K I -K R : ~2-20 μM) with an average Hill-slope of ~2. We determined that, at lower concentrations, CBG predominantly blocks sodium G max and slows recovery from inactivation. However, as the concentration is increased, CBG also induces a hyperpolarizing shift in the half-voltage of inactivation. Our modelling and multielectrode array recordings suggest that CBG attenuates DRG excitability. Conclusions and implications: Inhibition of Na v 1.7 channels in DRG neurons may underlie CBG-induced neuronal hypoexcitability. As most Na v 1.7 channels are inactivated at the resting membrane potential of DRG neurons, they are more likely to be inhibited by lower CBG concentrations, suggesting functional selectivity against Na v 1.7 channels, compared with other Na v channels (via G max block).
- Journal
- Br J Pharmacol
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Inhibition of sodium conductance by cannabigerol contributes to a reduction of dorsal root ganglion neuron excitability
- Bilingual Status
- semi_complete