TRPV1 in Cell Signaling: Molecular Mechanisms of Function and Modulation

Rosenbaum, Tamara; Jara-Oseguera, Andrés

doi:10.1007/978-94-007-5073-9_3

Cited by 1 publication

(1 citation statement)

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“…Recently, Eberhardt et al [28] reported that both parabenzoquinone (pBQ) and NAPQI can activate TRPV1. Furthermore, TRPA1 can co-express with TRPV1 on most of the sensory neurons in the liver, spinal cord, and kidney [15, 29]. In addition, the analgesia effect mediated by the activation of TRPA1 has been reported to be similar to that of TRPV1 [30, 31].…”

Section: Introductionmentioning

confidence: 99%

An insight into paracetamol and its metabolites using molecular docking and molecular dynamics simulation

Wang

Lin

et al. 2018

J Mol Model

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Paracetamol is a relatively safe analgesia/antipyretic drug without the risks of addiction, dependence, tolerance, and withdrawal when used alone. However, when administrated in an opioid/paracetamol combination product, which often contains a large quantity of paracetamol, it can be potentially dangerous due to the risk of hepatotoxicity. Paracetamol is known to be metabolized into N-(4-hydroxyphenyl)-arachidonamide (AM404) via fatty acid amide hydrolase (FAAH) and into N-acetyl-p-benzoquinone imine (NAPQI) via cytochrome P450 (CYP) enzymes. However, the underlying mechanism of paracetamol is still unclear. In addition, paracetamol has the potential to interact with other drugs that are also involved with CYP family enzymes (inducer/inhibitor/substrate), an example being illicit drugs. In our present work, we looked into the relationship between paracetamol and its metabolites (AM404 and NAPQI) using molecular docking and molecular dynamics (MD) simulations. We first carried out a series of molecular docking studies between paracetamol/AM404/NAQPI and their reported targets, including CYP 2E1, FAAH, TRPA1, CB1, and TRPV1. Subsequently, we performed MD simulations and energy decomposition for CB1-AM404, TRPV1-AM404, and TRPV1-NAPQI for further investigation of the dynamics interactions. Finally, we summarized and discussed the reported drug-drug interactions between paracetamol and central nervous system drugs, especially illicit drugs. Overall, we are able to provide new insights into the structural and functional roles of paracetamol and its metabolites that can inform the potential prevention and treatment of paracetamol overdose. Graphical abstract Paracetamol and its metabolites.

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