γ-Terpinene complexed with ß-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block.
J Pharm Pharmacol
; 74(11): 1629-1639, 2022 Nov 04.
Article
in En
| MEDLINE
| ID: mdl-35976257
ABSTRACT
OBJECTIVES:
Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in ß-cyclodextrin (γ-TPN/ß-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.METHODS:
The γ-TPN/ß-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, γ-TPN 50 mg/kg, γ-TPN/ß-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-α and IL-1ß levels, iNOS and c-Fos activity. The effects of γ-TPN on calcium channels were studied by patch-clamp and molecular docking.RESULTS:
ß-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1ß, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.CONCLUSION:
These results indicate that the complexation of γ-TPN into ß-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta-Cyclodextrins
/
Cancer Pain
/
Neoplasms
Limits:
Animals
Language:
En
Journal:
J Pharm Pharmacol
Year:
2022
Document type:
Article
Affiliation country:
Brazil