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Canna~Fangled Abstracts

On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence

By November 6, 2021November 8th, 2021No Comments
Review
. 2021 Nov 6.

doi: 10.1007/s12640-021-00424-z.

Online ahead of print.
Karen Jaqueline Paredes-Ruiz 1 2, Karla Chavira-Ramos 1 2, Mario Orozco-Morales 3, Cimen Karasu 4, Alexey A Tinkov 5, Michael Aschner 5 6, Abel Santamaría 7, Ana Laura Colín-González 8
Affiliations 

Abstract

The endocannabinoid system (ECS) is composed of endogenous cannabinoids; components involved in their synthesis, transport, and degradation; and an expansive variety of cannabinoid receptors. Hypofunction or deregulation of the ECS is related to pathological conditions. Consequently, endogenous enhancement of endocannabinoid levels and/or regulation of their metabolism represent promising therapeutic approaches. Several major strategies have been suggested for the modulation of the ECS: (1) blocking endocannabinoids degradation, (2) inhibition of endocannabinoid cellular uptake, and (3) pharmacological modulation of cannabinoid receptors as potential therapeutic targets. Here, we focused in this review on degradation/reuptake inhibitors over cannabinoid receptor modulators in order to provide an updated synopsis of contemporary evidence advancing mechanisms of endocannabinoids as pharmacological tools with therapeutic properties for the treatment of several disorders. For this purpose, we revisited the available literature and reported the latest advances regarding the biomedical properties of fatty acid amide hydrolase and monoacylglycerol lipase inhibitors in pre-clinical and clinical studies. We also highlighted anandamide and 2-arachidonoylglycerol reuptake inhibitors with promising results in pre-clinical studies using in vitro and animal models as an outlook for future research in clinical trials.

 

Keywords: 2-Aranchidonoylglycerol, Anandamide, Endocannabinoid metabolism, Endocannabinoid system, FAAH inhibitors; MAGL inhibitors

References

    1. Aaltonen N, Kedzierska E, Orzelska-Górka J, Lehtonen M, Navia-Paldanius D, Jakupovic H, Savinainen JR, Nevalainen T, Laitinen JT, Parkkari T, Gynther M (2016) In vivo characterization of the ultrapotent monoacylglycerol lipase inhibitor {4-[bis-(benzo[d][1,3]dioxol-5-yl)methyl]-piperidin-1-yl}(1H–1,2,4-triazol-1-yl)methanone (JJKK-048). J Pharmacol Exp Ther 359:62–72 – PubMed
    1. Abush H, Akirav I (2010) Cannabinoids modulate hippocampal memory and plasticity. Hippocampus 20:1126–1138 – PubMed
    1. Aghazadeh Tabrizi M, Baraldi PG, Ruggiero E, Saponaro G, Baraldi S, Romagnoli R, Martinelli A, Tuccinardi T (2015) Pyrazole phenylcyclohexylcarbamates as inhibitors of human fatty acid amide hydrolases (FAAH). Eur J Med Chem 97:289–305 – PubMed
    1. Adamczyk P, Gołda A, McCreary AC, Filip M, Przegaliński E (2008) Activation of endocannabinoid transmission induces antidepressant-like effects in rats. J Physiol Pharmacol 59:217–228 – PubMed
    1. Ahn K, Johnson DS, Mileni M, Beidler D, Long JZ, McKinney MK, Weerapana E, Sadagopan N, Liimatta M, Smith SE, Lazerwith S, Stiff C, Kamtekar S, Bhattacharya K, Zhang Y, Swaney S, Van Becelaere K, Stevens RC, Cravatt BF (2009) Discovery and characterization of a highly selective FAAH inhibitor that reduces inflammatory pain. Chem Biol 16:411–420 – PubMed – PMC

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