gamma-Terpinene complexed with beta-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block

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Pina, Licia T. S. ; Rabelo, Thallita K. ; Trindade, Gabriela G. G. ; Almeida, Iggo K. S. ; Oliveira, Marlange A. ; dos Santos, Priscila L. ; Souza, Diego Santos ; de Menezes-Filho, Jose E. R. ; Lins de Vasconcelos, Carla Maria ; Santos, Sandra L. ; Scotti, Luciana ; Scotti, Marcus T. ; Araujo, Adriano A. S. ; Quintans, Jullyana S. S. ; Quintans Junior, Lucindo J. ; Guimaraes, Adriana G.

• Document type: Journal article
• Source: Journal of Pharmacy and Pharmacology; v. 74, n. 11, p. 11-pg., 2022-08-17.

Abstract

Objectives Considering that gamma-terpinene (gamma-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in beta-cyclodextrin (gamma-TPN/beta-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved. Methods The gamma-TPN/beta-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, gamma-TPN 50 mg/kg, gamma-TPN/beta-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-alpha and IL-1 beta levels, iNOS and c-Fos activity. The effects of gamma-TPN on calcium channels were studied by patch-clamp and molecular docking. Results beta-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of gamma-TPN. This compound also reduced the levels of IL-1 beta, TNF-alpha 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 gamma-TPN into beta-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels. (AU)

• FAPESP's process: 19/18918-0 - Role of nitric oxide in cardiac arrhythmias during Hypothyroidism
• Grantee: Diego Santos de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral