N-Arachidonoyl dopamine

N-Arachidonoyl dopamine

Names
Preferred IUPAC name (5Z,8Z,11Z,14Z)-N-[2-(3,4-Dihydroxyphenyl)ethyl]icosa-5,8,11,14-tetraenamide
Other names NADA
Identifiers
CAS Number	199875-69-9 N
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL138921 Y
ChemSpider	4445314 Y
IUPHAR/BPS	4261
PubChem CID	5282105
CompTox Dashboard (EPA)	DTXSID70415208
InChI InChI=1S/C28H41NO3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-28(32)29-23-22-25-20-21-26(30)27(31)24-25/h6-7,9-10,12-13,15-16,20-21,24,30-31H,2-5,8,11,14,17-19,22-23H2,1H3,(H,29,32)/b7-6-,10-9-,13-12-,16-15- Y Key: MVVPIAAVGAWJNQ-DOFZRALJSA-N Y InChI=1/C28H41NO3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-28(32)29-23-22-25-20-21-26(30)27(31)24-25/h6-7,9-10,12-13,15-16,20-21,24,30-31H,2-5,8,11,14,17-19,22-23H2,1H3,(H,29,32)/b7-6-,10-9-,13-12-,16-15- Key: MVVPIAAVGAWJNQ-DOFZRALJBM
SMILES CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCC1=CC(=C(C=C1)O)O
Properties
Chemical formula	C28H41NO3
Molar mass	439.63 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

N-Arachidonoyl dopamine (NADA) is an endocannabinoid that acts as an agonist of the CB₁ receptor and the transient 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 the hippocampus, cerebellum, and striatum.^[2] It activates the TRPV1 channel with an EC₅₀ of approximately of 50 nM which makes it the putative endogenous 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]

See also

• Endocannabinoid

References

External links

• General information about NADA.