{{Chembox <!-- Images --> | ImageFile = Barettin.svg | ImageClass = skin-invert-image | ImageSize = 250px | ImageAlt = <!-- Names --> | IUPACName = | OtherNames = <!-- Sections --> | Section1 = {{Chembox Identifiers | CASNo = 104311-70-8 | PubChem = 11177588 | ChEMBL = 255898 | ChemSpiderID = 9352680 | StdInChI=1S/C17H19BrN6O2/c18-10-3-4-11-9(8-22-13(11)7-10)6-14-16(26)23-12(15(25)24-14)2-1-5-21-17(19)20/h3-4,6-8,12,22H,1-2,5H2,(H,23,26)(H,24,25)(H4,19,20,21)/b14-6-/t12-/m0/s1 | StdInChIKey = YYFNNPXWRXQUPR-JVXNRYDGSA-N | SMILES = C1=CC2=C(C=C1Br)NC=C2C=C3C(=O)NC(C(=O)N3)CCCN=C(N)N }} | Section2 = {{Chembox Properties | Formula = |C=17|H=19|Br=1|N=6|O=2 | MolarMass = | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = }} | Section3 = {{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}
'''Barettin''' is a brominated alkaloid made of a dehydrogenated brominated derivative of tryptophan linked by two peptide bonds to an arginine residue, forming a 2,5-diketopiperazine nucleus.<ref name="Lidgren 1986">{{Cite journal|last1=Lidgren|first1=Göran|last2=Bohlin|first2=Lars|last3=Bergman|first3=Jan|date=January 1986|title=Studies of swedish marine organisms VII. A novel biologically active indole alkaloid from the sponge Geodia baretti|journal=Tetrahedron Letters|volume=27|issue=28|pages=3283–3284|doi=10.1016/s0040-4039(00)84776-0|issn=0040-4039}}</ref><ref name="Sölter 2002">{{Cite journal|last1=Sölter|first1=Susanne|last2=Dieckmann|first2=Ralf|last3=Blumenberg|first3=Martin|last4=Francke|first4=Wittko|date=April 2002|title=Barettin, revisited?|journal=Tetrahedron Letters|volume=43|issue=18|pages=3385–3386|doi=10.1016/s0040-4039(02)00470-7|issn=0040-4039}}</ref> It is a cyclic dipeptide and a cyclized tryptamine. The compound occurs naturally in certain sea sponges<ref name="SjögrenGöranssonJohnson2004" /> and is known to interact with certain serotonin receptors.<ref name="SeekinsCárdenasStreicher2025" />
==Natural occurrence== Barettin is the major compound in the deep-sea sponge ''Geodia barretti''.<ref name="SjögrenGöranssonJohnson2004">{{Cite journal|last1=Sjögren|first1=Martin|last2=Göransson|first2=Ulf|last3=Johnson|first3=Ann-Louise|last4=Dahlström|first4=Mia|last5=Andersson|first5=Rolf|last6=Bergman|first6=Jan|last7=Jonsson|first7=Per R.|last8=Bohlin|first8=Lars|date=March 2004|title=Antifouling Activity of Brominated Cyclopeptides from the Marine SpongeGeodia barretti|journal=Journal of Natural Products|language=en|volume=67|issue=3|pages=368–372|doi=10.1021/np0302403|pmid=15043412|issn=0163-3864}}</ref> It was isolated for the first time in 1986 by Göran Lidgren, Lars Bohlin and Jan Bergman at Uppsala University, Sweden<ref name="Lidgren 1986" /> but the correct chemical structure was determined later in 2002.<ref name="Sölter 2002" /> Barettin is written with one 'r' because the authors misspelled ''Geodia barretti'' with one 'r' in the original paper.<ref name="Lidgren 1986" />
==Pharmacology== [[File:Geodia barretti.jpg|thumb|left|''Geodia barretti'' (dried specimen).]]
Barettin shows affinity for the serotonin 5-HT<sub>2</sub> receptors.<ref name="SeekinsCárdenasStreicher2025">{{cite journal | last=Seekins | first=Caleb | last2=Cárdenas | first2=Paco | last3=Streicher | first3=John | last4=Cartmell | first4=Chris | title=Analgesic Properties of the Natural Product Barettin Are Mediated by the 5HT2A/C Receptors (Abstract ID: 165920) | journal=The Journal of Pharmacology and Experimental Therapeutics | volume=392 | issue=3 | date=2025 | doi=10.1016/j.jpet.2024.101346 | article-number=101346 | url=https://linkinghub.elsevier.com/retrieve/pii/S0022356524429959 | access-date=12 April 2025| url-access=subscription }}</ref> It has analgesic effects that are reversed by the serotonin 5-HT<sub>2A</sub> receptor ketanserin, suggesting that barettin's analgesic effects may be mediated by serotonin 5-HT<sub>2A</sub> receptor signaling.<ref name="SeekinsCárdenasStreicher2025" /> Subsequently, barettin was found to act as an inverse agonist of the serotonin 5-HT<sub>2A</sub> receptor, with this action mediating its analgesic effects.<ref name="SeekinsOkineForrest2026">{{cite journal | vauthors = Seekins CA, Okine M, Forrest EG, Chavez T, Stump A, Kaleeswaran V, Carr JE, Hulme C, Cardenas P, Vanderah TW, Streicher JM, Cartmell C | title = Barettin, a Nonopioid, Nonhallucinogenic Marine Natural Product with Antihyperalgesic Properties Mediated by 5HT2A Inverse Agonism | journal = J Nat Prod | volume = | issue = | pages = | date = March 2026 | pmid = 41914263 | doi = 10.1021/acs.jnatprod.6c00169 | url = | doi-access = free }}</ref> In accordance with its lack of activation of the serotonin 5-HT<sub>2A</sub> receptor, barettin failed to produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.<ref name="SeekinsOkineForrest2026" />
Barettin seems to show antioxidant and anti-inflammatory properties which could be userful in treating diseases that affect the immune system and diseases that are caused by inflammation.<ref name="Lind 2013">{{Cite journal|last1=Lind|first1=Karianne F.|last2=Hansen|first2=Espen|last3=Østerud|first3=Bjarne|last4=Eilertsen|first4=Karl-Erik|last5=Bayer|first5=Annette|last6=Engqvist|first6=Magnus|last7=Leszczak|first7=Kinga|last8=Jørgensen|first8=Trond Ø.|last9=Andersen|first9=Jeanette H.|date=2013-07-22|title=Antioxidant and Anti-Inflammatory Activities of Barettin|journal=Marine Drugs|volume=11|issue=7|pages=2655–2666|doi=10.3390/md11072655|issn=1660-3397|pmc=3736444|pmid=23880935|doi-access=free}}</ref> Atherosclerosis, a disease characterized by stiffening and a buildup of compounds in arteries,<ref>{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/arteriosclerosis-atherosclerosis/symptoms-causes/syc-20350569|title=Arteriosclerosis / atherosclerosis - Symptoms and causes|work=Mayo Clinic|access-date=2018-12-01|language=en}}</ref> may be prevented by barettin due to its anti-inflammatory properties.<ref name="Lind 2013" /> The effects barettin has on inflammation may be due to its inhibitory properties on two protein kinases, receptor-interacting serine/threonine kinase 2 (RIPK2) and calcium/calmodulin-dependent protein kinase 1α (CAMK1α).<ref>{{Cite journal|last1=Lind|first1=Karianne Fredenfeldt|last2=Østerud|first2=Bjarne|last3=Hansen|first3=Espen|last4=Jørgensen|first4=Trond Ø|last5=Andersen|first5=Jeanette Hammer|date=2015|title=The immunomodulatory effects of barettin and involvement of the kinases CAMK1α and RIPK2|journal=Immunopharmacology and Immunotoxicology|volume=37|issue=5|pages=458–464|doi=10.3109/08923973.2015.1082584|issn=1532-2513|pmid=26466644|s2cid=21255063}}</ref>
==See also== * Substituted tryptamine
== References == {{Reflist}}
{{Serotonin receptor modulators}} {{Tryptamines}}
Category:5-HT2A antagonists Category:Alkene derivatives Category:Analgesics Category:Bromoarenes Category:Diketopiperazines Category:Guanidine alkaloids Category:Halogen-containing alkaloids Category:Indole alkaloids Category:Inverse agonists Category:Tryptamines