{{short description|Chemical compound}}

{{DISPLAYTITLE:''N''-Arachidonoyl dopamine}}

{{chembox

| Verifiedfields = changed

| verifiedrevid = 477503651

| Name=''N''-Arachidonoyl dopamine

| ImageFile = N-Arachidonoyl dopamine.svg

| ImageSize = 220px

| ImageFile2 = N-arachidonoyl dopamine 3D BS.png

| ImageSize2 = 220px

| PIN = (5''Z'',8''Z'',11''Z'',14''Z'')-''N''-[2-(3,4-Dihydroxyphenyl)ethyl]icosa-5,8,11,14-tetraenamide

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 4261

| CASNo_Ref = {{cascite|changed|??}}

| CASNo = 199875-69-9

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 138921

| PubChem = 5282105

| SMILES = CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCC1=CC(=C(C=C1)O)O

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4445314

| 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-

| InChIKey = MVVPIAAVGAWJNQ-DOFZRALJBM

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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-

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = MVVPIAAVGAWJNQ-DOFZRALJSA-N

| MeSHName =

|Section2={{Chembox Properties

| Formula = C₂₈H₄₁NO₃

| MolarMass = 439.63 g/mol

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

'''''N''-Arachidonoyl dopamine''' ('''NADA''') is an [[endocannabinoid]] that acts as an [[agonist]] of the [[Cannabinoid receptor type 1|CB₁ receptor]] <nowiki/>and the [[TRPV1|transient receptor potential V1]] (TRPV1) [[ion channel]]. NADA was first described as a putative endocannabinoid (agonist for the CB₁ receptor) in 2000<ref name=":0">{{Cite journal|title = N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo|journal = The Biochemical Journal|date = 2000-11-01|issn = 0264-6021|pmc = 1221424|pmid = 11042139|pages = 817–824|volume = 351|first1 = T.|last1 = Bisogno|first2 = D.|last2 = Melck|first3 = null|last3 = Bobrov MYu|first4 = N. M.|last4 = Gretskaya|first5 = V. V.|last5 = Bezuglov|first6 = L.|last6 = De Petrocellis|first7 = V.|last7 = Di Marzo|doi=10.1042/bj3510817|issue=3}}</ref> and was subsequently identified as an endovanilloid (agonist for TRPV1) in 2002.<ref name="Huang 8400–8405">{{cite journal | last1=Huang | first1=Susan M. | last2=Bisogno | first2=Tiziana | last3=Trevisani | first3=Marcello | last4=Al-Hayani | first4=Abdulmonem | last5=Petrocellis | first5=Luciano De | last6=Fezza | first6=Filomena | last7=Tognetto | first7=Michele | last8=Petros | first8=Timothy J. | last9=Krey | first9=Jocelyn F. | last10=Chu | first10=Constance J. | last11=Miller | first11=Jeffrey D. | last12=Davies | first12=Stephen N. | last13=Geppetti | first13=Pierangelo | last14=Walker | first14=J. Michael | last15=Marzo | first15=Vincenzo Di | title=An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors | journal=Proceedings of the National Academy of Sciences of the United States of America | volume=99 | issue=12 | date=2002-06-11 | pmid=12060783 | doi=10.1073/pnas.122196999| pmc=123079 | pages=8400–8405| bibcode=2002PNAS...99.8400H | doi-access=free }}</ref> NADA is an endogenous arachidonic acid based lipid found in the brain of rats, with especially high concentrations in the [[hippocampus]], [[cerebellum]], and [[striatum]].<ref name="Huang 8400–8405"/> It activates the TRPV1 channel with an [[EC50|EC₅₀]] of approximately of 50&nbsp;nM which makes it the putative [[endogenous]] TRPV1 agonist.<ref name="Huang 8400–8405"/>

In mice, NADA was shown to induce the tetrad of physiological paradigms associated with cannabinoids: hypothermia, hypo-locomotion, catalepsy, and analgesia.<ref name=":0" /><ref>{{Cite journal|title = Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine|journal = Bioorganic & Medicinal Chemistry Letters|date = 2001-02-26|issn = 0960-894X|pmid = 11229744|pages = 447–449|volume = 11|issue = 4|first1 = V.|last1 = Bezuglov|first2 = M.|last2 = Bobrov|first3 = N.|last3 = Gretskaya|first4 = A.|last4 = Gonchar|first5 = G.|last5 = Zinchenko|first6 = D.|last6 = Melck|first7 = T.|last7 = Bisogno|first8 = V.|last8 = Di Marzo|first9 = D.|last9 = Kuklev|doi=10.1016/s0960-894x(00)00689-2}}</ref><ref>{{Cite journal|title = Pharmacology and stereoselectivity of structurally novel cannabinoids in mice|journal = The Journal of Pharmacology and Experimental Therapeutics|date = 1988-12-01|issn = 0022-3565|pmid = 2849657|pages = 1046–1051|volume = 247|issue = 3|first1 = P. J.|last1 = Little|first2 = D. R.|last2 = Compton|first3 = M. R.|last3 = Johnson|first4 = L. S.|last4 = Melvin|first5 = B. R.|last5 = Martin}}</ref> NADA has been found to play a regulatory role in both the peripheral and central nervous systems, and displays antioxidant and neuroprotectant properties.<ref name="Huang 8400–8405"/><ref name="Price 1118–1130">{{Cite journal|title = Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide|journal = British Journal of Pharmacology|date = 2004-04-01|issn = 0007-1188|pmc = 1574881|pmid = 15006899|pages = 1118–1130|volume = 141|issue = 7|doi = 10.1038/sj.bjp.0705711|first1 = Theodore J.|last1 = Price|first2 = Amol|last2 = Patwardhan|first3 = Armen N.|last3 = Akopian|first4 = Kenneth M.|last4 = Hargreaves|first5 = Christopher M.|last5 = Flores}}</ref><ref>{{Cite journal|title = N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors|journal = Neuropsychopharmacology|date = 2007-02-01|issn = 0893-133X|pmid = 16760924|pages = 298–308|volume = 32|issue = 2|doi = 10.1038/sj.npp.1301118|first1 = Silvia|last1 = Marinelli|first2 = Vincenzo|last2 = Di Marzo|first3 = Fulvio|last3 = Florenzano|first4 = Filomena|last4 = Fezza|first5 = Maria Teresa|last5 = Viscomi|first6 = Mario|last6 = van der Stelt|first7 = Giorgio|last7 = Bernardi|first8 = Marco|last8 = Molinari|first9 = Mauro|last9 = Maccarrone|doi-access = free}}</ref><ref>{{Cite journal|title = TRPV1 and CB(1) receptor-mediated effects of the endovanilloid/endocannabinoid N-arachidonoyl-dopamine on primary afferent fibre and spinal cord neuronal responses in the rat|journal = The European Journal of Neuroscience|date = 2004-07-01|issn = 0953-816X|pmid = 15245490|pages = 175–184|volume = 20|issue = 1|doi = 10.1111/j.1460-9568.2004.03481.x|first1 = Devi R.|last1 = Sagar|first2 = Paul A.|last2 = Smith|first3 = Paul J.|last3 = Millns|first4 = Darren|last4 = Smart|first5 = David A.|last5 = Kendall|first6 = Victoria|last6 = Chapman|s2cid = 42626601}}</ref> NADA has also been implicated in smooth muscle contraction and vasorelaxation in blood vessels.<ref>{{Cite journal|title = Antioxidant and neuroprotective properties of N-arachidonoyldopamine|journal = Neuroscience Letters|date = 2008-01-24|issn = 0304-3940|pmid = 18069125|pages = 6–11|volume = 431|issue = 1|doi = 10.1016/j.neulet.2007.11.010|first1 = Mikhail Yu|last1 = Bobrov|first2 = Anatoly A.|last2 = Lizhin|first3 = Ekaterina L.|last3 = Andrianova|first4 = Natalia M.|last4 = Gretskaya|first5 = Lidia E.|last5 = Frumkina|first6 = Leonid G.|last6 = Khaspekov|first7 = Vladimir V.|last7 = Bezuglov|s2cid = 23436811}}</ref><ref>{{Cite journal|title = Capsaicin-like effects of N-arachidonoyl-dopamine in the isolated guinea pig bronchi and urinary bladder|journal = European Journal of Pharmacology|date = 2003-08-15|issn = 0014-2999|pmid = 12954366|pages = 107–114|volume = 475|issue = 1–3|first1 = Selena|last1 = Harrison|first2 = Luciano|last2 = De Petrocellis|first3 = Marcello|last3 = Trevisani|first4 = Francesca|last4 = Benvenuti|first5 = Maurizio|last5 = Bifulco|first6 = Pierangelo|last6 = Geppetti|first7 = Vincenzo|last7 = Di Marzo|doi=10.1016/s0014-2999(03)02114-9}}</ref><ref>{{Cite journal|title = Characterisation of the vasorelaxant properties of the novel endocannabinoid N-arachidonoyl-dopamine (NADA)|journal = British Journal of Pharmacology|date = 2004-03-01|issn = 0007-1188|pmc = 1574254|pmid = 14769783|pages = 803–812|volume = 141|issue = 5|doi = 10.1038/sj.bjp.0705643|first1 = Saoirse E.|last1 = O'Sullivan|first2 = David A.|last2 = Kendall|first3 = Michael D.|last3 = Randall}}</ref><ref>{{Cite journal|title = Time-dependent vascular effects of Endocannabinoids mediated by peroxisome proliferator-activated receptor gamma (PPARγ)|journal = PPAR Research|date = 2009-01-01|issn = 1687-4757|pmc = 2676321|pmid = 19421417|pages = 425289|volume = 2009|doi = 10.1155/2009/425289|first1 = Saoirse E.|last1 = O'Sullivan|first2 = David A.|last2 = Kendall|first3 = Michael D.|last3 = Randall|doi-access = free}}</ref> 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).<ref>{{Cite journal|title = Opposite effects of anandamide and N-arachidonoyl dopamine in the regulation of prostaglandin E and 8-iso-PGF formation in primary glial cells|journal = Journal of Neurochemistry|date = 2009-04-01|issn = 1471-4159|pmid = 19200337|pages = 452–464|volume = 109|issue = 2|doi = 10.1111/j.1471-4159.2009.05966.x|first1 = Carmen M.|last1 = Navarrete|first2 = Bernd L.|last2 = Fiebich|first3 = Amaya García|last3 = de Vinuesa|first4 = Sandra|last4 = Hess|first5 = Antonio C. P.|last5 = de Oliveira|first6 = Eduardo|last6 = Candelario-Jalil|first7 = Francisco J.|last7 = Caballero|first8 = Marco A.|last8 = Calzado|first9 = Eduardo|last9 = Muñoz|s2cid = 205620351|doi-access = }}</ref><ref>{{Cite journal|title = Endogenous N-acyl-dopamines induce COX-2 expression in brain endothelial cells by stabilizing mRNA through a p38 dependent pathway|journal = Biochemical Pharmacology|date = 2010-06-15|issn = 1873-2968|pmid = 20206142|pages = 1805–1814|volume = 79|issue = 12|doi = 10.1016/j.bcp.2010.02.014|first1 = Carmen M.|last1 = Navarrete|first2 = Moisés|last2 = Pérez|first3 = Amaya García|last3 = de Vinuesa|first4 = Juan A.|last4 = Collado|first5 = Bernd L.|last5 = Fiebich|first6 = Marco A.|last6 = Calzado|first7 = Eduardo|last7 = Muñoz}}</ref><ref>{{Cite journal|title = Immunosuppressive activity of endovanilloids: N-arachidonoyl-dopamine inhibits activation of the NF-kappa B, NFAT, and activator protein 1 signaling pathways|journal = Journal of Immunology|date = 2004-02-15|issn = 0022-1767|pmid = 14764703|pages = 2341–2351|volume = 172|issue = 4|first1 = Rocío|last1 = Sancho|first2 = Antonio|last2 = Macho|first3 = Laureano|last3 = de La Vega|first4 = Marco A.|last4 = Calzado|first5 = Bernd L.|last5 = Fiebich|first6 = Giovanni|last6 = Appendino|first7 = Eduardo|last7 = Muñoz|doi=10.4049/jimmunol.172.4.2341|doi-access = free}}</ref> 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.<ref>{{Cite journal|title = The endocannabinoid/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells|journal = The Journal of Biological Chemistry|date = 2014-05-09|issn = 1083-351X|pmc = 4036321|pmid = 24644287|pages = 13079–13100|volume = 289|issue = 19|doi = 10.1074/jbc.M113.536953|first1 = Kevin|last1 = Wilhelmsen|first2 = Samira|last2 = Khakpour|first3 = Alphonso|last3 = Tran|first4 = Kayla|last4 = Sheehan|first5 = Mark|last5 = Schumacher|first6 = Fengyun|last6 = Xu|first7 = Judith|last7 = Hellman|doi-access = free}}</ref> It can increase the TRPV1-mediated release of substance P and calcitonin gene-related peptide (CGRP) in rat dorsal spinal cord slices.<ref name="Huang 8400–8405"/> Furthermore, NADA also displays inhibitory activity in HIV-1 replication assays.<ref>{{Cite journal|title = Mechanisms of HIV-1 inhibition by the lipid mediator N-arachidonoyldopamine|journal = Journal of Immunology|date = 2005-09-15|issn = 0022-1767|pmid = 16148147|pages = 3990–3999|volume = 175|issue = 6|first1 = Rocío|last1 = Sancho|first2 = Laureano|last2 = de la Vega|first3 = Antonio|last3 = Macho|first4 = Giovanni|last4 = Appendino|first5 = Vincenzo|last5 = Di Marzo|first6 = Eduardo|last6 = Muñoz|doi=10.4049/jimmunol.175.6.3990|doi-access = free}}</ref> Finally, NADA can prevent the degranulation and release of TNF from RBL- 2H3 mast cells treated with an IgE-antigen complex.<ref>{{Cite journal|title = Inhibitory effect of N-Acyl dopamines on IgE-mediated allergic response in RBL-2H3 cells|journal = Lipids|date = 2013-04-01|issn = 1558-9307|pmid = 23377981|pages = 383–393|volume = 48|issue = 4|doi = 10.1007/s11745-013-3758-6|first1 = Jae-Myung|last1 = Yoo|first2 = Eun Seok|last2 = Park|first3 = Mee Ree|last3 = Kim|first4 = Dai-Eun|last4 = Sok|s2cid = 3995567}}</ref> 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.<ref>{{cite journal | title=The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine | journal=Prostaglandins, Leukotrienes and Essential Fatty Acids | volume=81 | issue=4 | date=2009-10-01 | issn=0952-3278 | doi=10.1016/j.plefa.2009.05.026 | pmid=19570666 | pages=291–301 | ref={{sfnref | Prostaglandins, Leukotrienes and Essential Fatty Acids | 2009}} | last1 = Shu-Jung Hu | first1 = Sherry | last2 = Bradshaw | first2 = Heather B. | last3 = Benton | first3 = Valery M. | last4 = Shih-Chieh Chen | first4 = Jay | last5 = Huang | first5 = Susan M. | last6 = Minassi | first6 = Alberto | last7 = Bisogno | first7 = Tiziana | last8 = Masuda | first8 = Kim | last9 = Tan | first9 = Bo | last10 = Roskoski | first10 = Robert | last11 = Cravatt | first11 = Benjamin F. | last12 = Di Marzo | first12 = Vincenzo | last13 = Walker | first13 = J. Michael| pmc=2757501 }}</ref> 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.).<ref>{{cite journal | last1=Pajouhesh | first1=H | last2=Hancock | first2=A J | title=Synthesis of cyclopentano-N-methylphosphatidylethanolamines: aminolysis during the use of methylamine. | journal=Journal of Lipid Research | volume=25 | issue=3 | date=1984-03-01 | issn=0022-2275 | pmid=6726084 | pages=310–312 | doi=10.1016/S0022-2275(20)37828-7 | url=http://www.jlr.org/content/25/3/310.abstract| access-date=2017-12-15| doi-access=free }}</ref>

== See also ==

* [[Endocannabinoid]]

== References ==

{{Reflist}}

== External links ==

* [https://web.archive.org/web/20110708130703/http://www.caymanchem.com/app/template/Product.vm/catalog/90057/tab/data/a/z General information] about NADA.

{{Cannabinoids}}

{{Neurotransmitters}}

{{Cannabinoidergics}}

{{Transient receptor potential channel modulators}}

{{DEFAULTSORT:Arachidonoyl dopamine, N-}}

[[Category:Endocannabinoids]]

[[Category:Vanilloids]]

[[Category:Eicosanoids]]

[[Category:Catechols]]

[[Category:Fatty acid amides]]

[[Category:CB1 receptor agonists]]

[[Category:Arachidonyl compounds]]