Interações do canabidiol no canal de cálcio dependente de voltagem por docking molecular
papel no seu mecanismo inibitório neuronal
DOI:
https://doi.org/10.56102/afmo.2023.283Palavras-chave:
Canabidiol, Analgésico, Modelagem de medicamentos, Canal de cálcio dependente de voltagemResumo
Objetivo: analisar as interações do canabidiol (CBD) no CaV3.2 através de docking molecular. Metodologia: trata-se de uma pesquisa do tipo in silico, que o CBD e a gabapentina (GBP) foram utilizadas como substâncias teste e o canal CaV3.2 como proteína alvo. Os experimentos de docking molecular foram realizados no Dockthor. As simulações dos fármacos foram classificadas em ordem de maior afinidade no canal. As energias de ligação foram comparadas usando o teste “t” no programa GraphPad Prism, os valores foram significantemente diferentes (p < 0,05). Resultados: as posições entre CBD e GBP foram 1.000,00 conformações. Os dados mostraram que as energias de ligação no CaV3.2 e CBD ou GBP foram - 6,493 ± 0,07 kcal/mol e - 6,842 ± 0,19 kcal/mol, respectivamente. Esses valores não apresentaram diferença estatística significante (p = 0,08), mostrando que ambos têm afinidade similar no canal, apesar de posicionamentos distintos. Conclusões: o CDB se liga ao CaV3.2, o que corrobora o bloqueio deste canal. Estes dados fundamentam o efeito analgésico do CDB pela via inibitória neuronal.
Referências
Witte W, Stein C. History, Definitions and Contemporary Viewpoins. In: Kopf A, Patel NB, editores. Guia para o gerenciamento da dor em configurações de poucos recursos. Seattle; IASP; 2010:3-8p.
Cipriano A, Almeida D, Vall J. Perfil do paciente com dor crônica atendido em um ambulatório de dor de uma grande cidade do sul do Brasil. Rev Dor. 2011;12(4):297-300.
Picavet HS, Schouten JS. Dor musculoesquelética na Holanda, prevalências, consequências e grupos de risco, estudo DMC (3). Dor. 2003;102(1-2):167-78.
Polacek C, Christopher R, Mann M, Udall M, Craig T, Deminski M, Sathe NA. Percepções dos profissionais de saúde sobre os desafios do manejo da dor crônica. Am J Manag Care. 2020;26:e135–e139.
Silva, LMN, Lopes, DC, Silva, EC. O uso fitoterápico do canabidiol no tratamento de dores crônicas: Uma revisão de literatura. SEMOC–Semana de Mobilização Científica-Economia Circular: o novo paradigma para a sustentabilidade, 2021.
Bih CI, Chen T, Nunn AVW, Bazelot M, Dallas M, Whalley BJ. Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics 2015;12:699–730.
De Petrocellis L, Ligresti A, Moriello AS, Allarà M, Bisogno T, Petrosino S, Stott CG, Di Marzo V. Effects of cannabinoids and cannabinoid-enriched cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. British Journal of Pharmacology. 2011;163(7):1479–1494. https://doi.org/10.1111/j.1476-5381.2010.01166.x
Ghovanloo MR, Shuart NG, Mezeyova J, Dean RA, Ruben PC, Goodchild SJ. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. The Journal of Biological Chemistry. 2018:293(43),16546–16558. https://doi.org/10.1074/jbc.RA118.004929
Ross HR, Napier I, Connor M. Inhibition of recombinant human T-type calcium channels by Delta9-tetrahydrocannabinol and cannabidiol. The Journal of Biological Chemistry. 2008;283(23),16124–16134. https://doi.org/10.1074/jbc.M707104200
Sait LG, Sula A, Ghovanloo MR, Hollingworth D, Ruben PC, Wallace BA. Cannabidiol interactions with voltage-gated sodium channels. eLife. 2020;9:e58593. https://doi.org/10.7554/eLife.58593
Patel RR, Barbosa C, Brustovetsky T, Brustovetsky N, Cummins TR. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol. Brain. 2016;139(8):2164–81.
Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The physiology, pathology, and pharmacology of voltage-gated calcium Channels and their future therapeutic potential, Pharm. Rev. 2015;67(4):821–870.
Choi S, Na HS, Kim J, Lee J, Lee S, Kim D, Park J, Chen CC, Campbell KP, Shin HS. Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav.2007;6(5):425–431. 12
Talley EM, Cribbs LL, Lee JH, Daud A, Perez-Reyes E, Bayliss DA. Differential distribution of three members of a gene family encoding low voltage-activated (Ttype) calcium channels, J. Neurosci.: Off. J. Soc. Neurosci. 1999;19(6):1895–1911.
Kamau PM, Li H, Yao Z, Han Y,Luo A, Zhang H, Boonyarat C, Yenjai C, Mwangi J, Zeng L, Yang S, Lai R, Luo L. Potent CaV3.2 channel inhibitors exert analgesic effects in acute and chronic pain models. Biomedicine & Pharmacotherapy. 2022;153:113310.
Jarvis MF, Scott VE, McGaraughty S, Chu KL, Xu J, Niforatos W, Milicic I, Joshi S, Zhang Q, Xia Z, A peripherally acting, selective T-type calcium channel blocker, ABT-639, effectively reduces nociceptive and neuropathic pain in rats, Biochem. Pharmacol. 2014;89(4):536–544.
Ziegler D, Duan WR, G. G, Thomas JW, Nothaft W. A randomized doubleblind, placebo-, and active-controlled study of T-type calcium channel blocker ABT-639 in patients with diabetic peripheral neuropathic pain. Pain. 2015;156(10):2013–2020.
Lee M. Z944: a first in class T-type calcium channel modulator for the treatment of pain, J. Peripher. Nerv. Syst. 2014;19(2):S11–S12.
Snutch TP, Zamponi GW. Recent advances in the development of T-type calcium channel blockers for pain intervention, Br. J. Pharmacol. 2018;175(12):2375–2383.
Teixeira LR, Silva Júnior JJ, Vieira PHS, Canto MVG, Figueirêdo AGM, Silva JLV. Tamoxifen inhibits the anion channel induced by Staphylococcus aureus α-hemolysin: electrophysiological and docking analysis. RSD [Internet], 2021;10(2):e13010212326.
Magalhães CS, et al. A dynamic niching genetic algorithm strategy for docking of highly flexible ligands. Information Sciences. 2014;289:206–24.
Liu ZL, Li L, Ma HL, Zhong QS, Ke JY, Zhang H. Mechanism of action of Zhishi Daozhi decoction in the treatment of diarrhea based on network pharmacology and molecular docking. Drug Combination Therapy. 2023;5(1):1-8. https://doi.org/10.53388/DCT20230003
Du G, Qu X, Hu J, Zhang Y, Cai Y. Identification of Taohong Siwu Decoction in Treating Chronic Glomerulonephritis Using Network Pharmacology and Molecular Docking. Natural Product Communications. 2022;17(11):1-12.
Silva Júnior GJ, Arruda GEJ, Lira NBD, Lira NBD, Costa AEA, Morioka CY, Silva JLV. Pharmacological prospection of cannabidiol analgesic action through molecular docking: interactions with voltage-gated sodium channel Nav1.7. RSD [Internet]. 2023;12(3):e30340292.
Mirlohi S, Bladen C, Santiago MJ, Arnold JC, McGregor I, Connor M. Inhibition of human recombinant T-type calcium channels by phytocannabinoids in vitro. British Journal of Pharmacology. 2022;179(15):4031–4043. https://doi.org/10.1111/bph.158429.
Gee NS, Brown JP, Dissanayake VU, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem. 1996;271:5768–76.
Russo M, Graham B, Santarelli DM. Gabapentin - Friend or foe?. Pain Practice. 2023;23:63–69.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2023 Gisele Evelin de Jesus Arruda, Gidelson José Silva Júnior, Nathalia Napoli Mendes, Gustavo Napoli Mendes, Alessandra Emertice de Almeida Costa, Luana Carmélia de Lira Fernandes, Joelmir Lucena Veiga da SilvaSilva
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Esta licença permite que outros distribuam, remixem, adaptem e desenvolvam seu trabalho, mesmo comercialmente, desde que creditem a revista pela criação original.
