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| Names | |
|---|---|
| Preferred IUPAC name (5Z,8Z,11Z,14Z)-N-[2-(3,4-Dihydroxyphenyl)ethyl]icosa-5,8,11,14-tetraenamide | |
| Other names NADA | |
| Identifiers | |
3D model (JSmol) | |
| ChEMBL | |
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| Properties | |
| C28H41NO3 | |
| Molar mass | 439.63 g/mol |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
N-Arachidonoyl dopamine (NADA) is anendocannabinoid that acts as anagonist of theCB1 receptor and thetransient receptor potential V1 (TRPV1)ion channel. NADA was first described as a putative endocannabinoid (agonist for the CB1 receptor) in 2000[1] and was subsequently identified as an endovanilloid (agonist for TRPV1) in 2002.[2] NADA is an endogenous arachidonic acid based lipid found in the brain of rats, with especially high concentrations in thehippocampus,cerebellum, andstriatum.[2] It activates the TRPV1 channel with anEC50 of approximately of 50 nM which makes it the putativeendogenous TRPV1 agonist.[2]
In mice, NADA was shown to induce the tetrad of physiological paradigms associated with cannabinoids: hypothermia, hypo-locomotion, catalepsy, and analgesia.[1][3][4] NADA has been found to play a regulatory role in both the peripheral and central nervous systems, and displays antioxidant and neuroprotectant properties.[2][5][6][7] NADA has also been implicated in smooth muscle contraction and vasorelaxation in blood vessels.[8][9][10][11] Additionally, NADA has been observed to suppress inflammatory activation of human Jurkat T cells and to inhibit the release of prostaglandin E2 (PGE2) from lipopolysaccharide (LPS)-activated astrocytes, microglia and mouse brain ECs (MEC-Brain).[12][13][14] NADA also promotes the inflammatory resolution of human endothelial cells activated by both endogenous (i.e. TNF) and exogenous (i.e. bacterial derived LPS (TLR4 agonist) and FSL-1 (TLR2/6 agonist)) inflammatory mediators.[15] It can increase the TRPV1-mediated release of substance P and calcitonin gene-related peptide (CGRP) in rat dorsal spinal cord slices.[2] Furthermore, NADA also displays inhibitory activity in HIV-1 replication assays.[16] Finally, NADA can prevent the degranulation and release of TNF from RBL- 2H3 mast cells treated with an IgE-antigen complex.[17] Together, these studies show that physiological functions attributed to NADA are multifaceted, and include the ability to modulate the immune response.
The biosynthetic pathway of N-arachindonoyldopamine is not well understood. It has been proposed to be conjugated from arachidonoyl-CoA or arachidonoyl phospholipids and dopamine, but in vitro experiments do not support this theory.[18] However, the indirect biosynthesis of phospholipid esters with dopamine may be possible, as dopamine can induce the aminolysis of the glycerol-fatty acid bonds in phospholipid chains (arachidonoyl, palmitoyl, linoleyl, etc.).[19]
