Canna~Fangled Abstracts

Endocannabinoid Metabolism and Transport as Drug Targets

By September 21, 2022September 26th, 2022No Comments


doi: 10.1007/978-1-0716-2728-0_16.

Affiliations 

Abstract

The wide distribution of the endocannabinoid system (ECS) throughout the body and its pivotal pathophysiological role offer promising opportunities for the development of novel therapeutic drugs for treating several diseases. However, the need for strategies to circumvent the unwanted psychotropic and immunosuppressive effects associated with cannabinoid receptor agonism/antagonism has led to considerable research in the field of molecular alternatives, other than type-1 and type-2 (CB1/2) receptors, as therapeutic targets to indirectly manipulate this pro-homeostatic system. In this context, the use of selective inhibitors of proteins involved in endocannabinoid (eCB) transport and metabolism allows for an increase or decrease of the levels of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) in the sites where these major eCBs are indeed needed. This chapter will briefly review some preclinical and clinical evidence for the therapeutic potential of ECS pharmacological manipulation.

Keywords: 2-Arachidonoylglycerol, Anandamide, Drug design, Metabolic routes, Signal transduction, Transport mechanisms

References

    1. Pacher P, Bátkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58:389. https://doi.org/10.1124/PR.58.3.2 – DOI – PubMed
    1. Hu W-R, Lian Y-F, Peng L-X, Lei J-J, Deng C-C, Xu M, Feng Q-S, Chen L-Z, Bei J-X, Zeng Y-X (2014) Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma. Int J Clin Exp Pathol 7:3704–3713 – PubMed – PMC
    1. Gong X, Zheng X, Huang Y, Song W, Chen G, Chen T (2022) Monoacylglycerol lipase (MAGL) inhibition impedes the osteosarcoma progression by regulating epithelial mesenchymal transition. Tohoku J Exp Med 256:19–26. https://doi.org/10.1620/TJEM.256.19 – DOI – PubMed
    1. Kokona D, Spyridakos D, Tzatzarakis M, Papadogkonaki S, Filidou E, Arvanitidis KI, Kolios G, Lamani M, Makriyannis A, Malamas MS et al (2021) The endocannabinoid 2-arachidonoylglycerol and dual ABHD6/MAGL enzyme inhibitors display neuroprotective and anti-inflammatory actions in the in vivo retinal model of AMPA excitotoxicity. Neuropharmacology 185:108450. https://doi.org/10.1016/J.NEUROPHARM.2021.108450 – DOI – PubMed
    1. Deng H, van der Stelt M (2018) Chemical tools to modulate 2-arachidonoylglycerol biosynthesis. Biotechnol Appl Biochem 65:9–15. https://doi.org/10.1002/bab.1568 – DOI – PubMed

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