{{chembox |Verifiedfields = changed |Watchedfields = changed |verifiedrevid = 415511050 |Name = Gramine |PIN = 1-(1''H''-Indol-3-yl)-''N'',''N''-dimethylmethanamine |OtherNames = donaxine |ImageFile_Ref = {{chemboximage|correct|??}} |ImageFile = Gramine.svg |ImageClass = skin-invert-image |ImageSize = 175px |ImageName = Chemical structure of gramine |Section1={{Chembox Identifiers |ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |ChemSpiderID = 6625 |ChEBI_Ref = {{ebicite|correct|EBI}} |ChEBI = 28948 |KEGG_Ref = {{keggcite|correct|kegg}} |KEGG = C08304 |InChI = 1/C11H14N2/c1-13(2)8-9-7-12-11-6-4-3-5-10(9)11/h3-7,12H,8H2,1-2H3 |InChIKey = OCDGBSUVYYVKQZ-UHFFFAOYAK |ChEMBL_Ref = {{ebicite|correct|EBI}} |ChEMBL = 254348 |PubChem = 6890 |EC_number = 201-749-8 |UNII = FGQ8A78L14 |StdInChI_Ref = {{stdinchicite|correct|chemspider}} |StdInChI = 1S/C11H14N2/c1-13(2)8-9-7-12-11-6-4-3-5-10(9)11/h3-7,12H,8H2,1-2H3 |StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |StdInChIKey = OCDGBSUVYYVKQZ-UHFFFAOYSA-N |CASNo_Ref = {{cascite|correct|??}} |CASNo = 87-52-5 |SMILES = c1cccc2c1c(c[nH]2)CN(C)C }} |Section2={{Chembox Properties |Formula = C<sub>11</sub>H<sub>14</sub>N<sub>2</sub> |MolarMass = 174.24 g/mol |MeltingPtC = 138 to 139 }} |Section7={{Chembox Hazards | NFPA-H = 2 | NFPA-R = 0 | NFPA-F = 1}} }}

'''Gramine''' (also called '''donaxine''') is a naturally occurring indole alkaloid present in several plant species. Gramine may play a defensive role in these plants, since it is toxic to many organisms.<ref name=barley>{{cite journal | author = Corcuera, L. J. | title = Biochemical Basis of the Resistance of the Barley to Aphids | journal = Phytochemistry | year = 1993 | volume = 33 | issue = 4 | pages = 741–747 | doi = 10.1016/0031-9422(93)85267-U}}</ref>

==Occurrence== Gramine has been found in the giant reed, ''Arundo donax'',<ref>{{cite journal | title = Über die Alkaloide von ''Arundo Donax'' L. |author1=Orechoff, A. |author2=Norkina, S. | journal = Berichte der Deutschen Chemischen Gesellschaft | year = 1935 | volume = 68 | issue = 3 | pages = 436–437 | doi = 10.1002/cber.19350680312}}</ref><ref name=toxicants/> ''Acer saccharinum'' (Silver Maple),<ref>{{cite journal |author1=Pachter, I. J. |author2=Zacharias, D. E. |author3=Ribeiro, O. | title = Indole Alkaloids of ''Acer saccharinum'' (the Silver Maple), ''Dictyoloma incanescens'', ''Piptadenia colubrina'', and ''Mimosa hostilis'' | journal = Journal of Organic Chemistry | year = 1959 | volume = 24 | issue = 9 | pages = 1285–1287 | doi = 10.1021/jo01091a032}}</ref> ''Hordeum'',<ref name=barley/><ref name=toxicants/> (a grass genus that includes barley) and ''Phalaris''<ref name=toxicants>{{cite book | title = Toxicants of Plant Origin, Alkaloids | page = 172 | author = Cheeke, P. R. | publisher = CRC Press | year = 1989 | isbn = 0-8493-6990-8 | url = https://books.google.com/books?id=eASgQyXq8xMC&pg=PA172}}</ref> (another grass genus).

==Effects and toxicity== Gramine is a close analogue of the psychedelic drug dimethyltryptamine (DMT), but its side chain has one less carbon atom in comparison.<ref name="BrimblecombePinder1975">{{cite book | vauthors = Brimblecombe RW, Pinder RM | chapter = Indolealkylamines and Related Compounds | pages = 98–144 | title = Hallucinogenic Agents | date = 1975 | publisher = Wright-Scientechnica | location = Bristol | isbn = 978-0-85608-011-1 | oclc = 2176880 | ol = OL4850660M | url = https://bitnest.netfirms.com/external/Books/978-0-85608-011-1 | quote = Other structural variations of interest include gramine (4.15), which contains only a one-carbon side-chain and is without significant behavioural activity (Gessner, Mcisaac, and Page, 1961; Ho, Mcisaac, An, Harris, Walker, Kralik, and Airaksinen, 1970).}}</ref> In contrast to DMT, gramine does not have significant psychedelic-like behavioral effects in animals.<ref name="BrimblecombePinder1975" /> The same is true of 5-methoxygramine (5-MeO-gramine), which failed to substitute for DOM in rodent drug discrimination tests.<ref name="GlennonYoungJacyno1983">{{cite journal | vauthors = Glennon RA, Young R, Jacyno JM, Slusher M, Rosecrans JA | title = DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines | journal = Eur J Pharmacol | volume = 86 | issue = 3–4 | pages = 453–459 | date = January 1983 | pmid = 6572591 | doi = 10.1016/0014-2999(83)90196-6 | url = }}</ref> The ''N'',''N''-didesmethyl analogue of gramine, indolemethylamine (3-aminomethylindole), showed 71-fold reduced potency as a serotonin receptor agonist compared to tryptamine in the rat stomach strip.<ref name="Vane1959">{{cite journal | vauthors = Vane JR | title = The relative activities of some tryptamine analogues on the isolated rat stomach strip preparation | journal = Br J Pharmacol Chemother | volume = 14 | issue = 1 | pages = 87–98 | date = March 1959 | pmid = 13651584 | pmc = 1481817 | doi = 10.1111/j.1476-5381.1959.tb00933.x | url = }}</ref>

Gramine has been found to act as an agonist of the adiponectin receptor 1 (AdipoR1).<ref name="pmid23691032">{{cite journal | vauthors = Sun Y, Zang Z, Zhong L, Wu M, Su Q, Gao X, Zan W, Lin D, Zhao Y, Zhang Z | title = Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay | journal = PLOS ONE | volume = 8 | issue = 5 | article-number = e63354 | year = 2013 | pmid = 23691032 | pmc = 3653934 | doi = 10.1371/journal.pone.0063354| bibcode = 2013PLoSO...863354S | doi-access = free }}</ref>

The LD50 of gramine is 44.6&nbsp;mg/ kg iv in mice and 62.9&nbsp;mg/ kg iv in rats.<ref>{{cite journal | author = Erspamer, V. | title = Pharmacology of Indolealkylamines | journal = Pharmacological Reviews | year = 1954 | volume = 6 | issue = 4 | pages = 425–487 | doi = 10.1016/S0031-6997(25)07372-7 | pmid = 13236482 | url = http://pharmrev.aspetjournals.org/content/6/4/425.abstract| url-access = subscription }}</ref> Numerous studies have been done on the toxicity of gramine and tryptamines to insects harmful to crops in order to assess their potential use as an insecticide.<ref>{{cite journal | author = Corcuera, L. J. | title = Effects of Indole Alkaloids from Gramineae on Aphids | journal = Phytochemistry | year = 1984 | volume = 23 | issue = 3 | pages = 539–541 | doi = 10.1016/S0031-9422(00)80376-3| bibcode = 1984PChem..23..539C | url = https://repositorio.uchile.cl/handle/2250/156743 }}</ref>

Recent toxicity evaluations show Gramine to be relatively low toxicity in humans, and to have anti-mutagenic and potential neuroprotective action, as a widely found alkaloid present in oats and barley.<ref> <i>"Safety evaluation of an oat grain alkaloid gramine by genotoxicity assays" </i>, Manash Pratim Pathak et al. Drug Chem Toxicol. 2018 Apr. https://pubmed.ncbi.nlm.nih.gov/28523965/ </ref>

==See also== * Dimethyltryptamine (DMT) * Dimethylhomotryptamine (DMHT)

==References== {{Reflist}}

Category:Adiponectin receptor agonists Category:Indole alkaloids Category:Dimethylamino compounds Category:Plant toxins