Harmane

{{short description|Chemical compound}} {{Chembox | ImageFile = Harmane.svg | ImageClass = skin-invert-image | ImageSize = 220px | ImageFile2 = Harmane 3D BS.png | ImageClass2 = bg-transparent | ImageSize2 = 220px | PIN = 1-Methyl-9''H''-pyrido[3,4-''b'']indole | OtherNames = Harman, 1-Methyl-β-carboline, Aribine, Aribin, Locuturine, Locuturin, Loturine, Passiflorin, 1-Methylnorharman, NSC 54439 |Section1={{Chembox Identifiers | CASNo = 486-84-0 | CASNo_Ref = {{cascite|correct|CAS}} | UNII = 82D6J0535P | UNII_Ref = {{fdacite|correct|FDA}} | PubChem = 5281404 | EINECS = 207-642-2 | ChemSpiderID = 4444755 | SMILES = CC1=NC=CC2=C1NC3=CC=CC=C23 | InChI = 1/C12H10N2/c1-8-12-10(6-7-13-8)9-4-2-3-5-11(9)14-12/h2-7,14H,1H3 | InChIKey = PSFDQSOCUJVVGF-UHFFFAOYAA | StdInChI = 1S/C12H10N2/c1-8-12-10(6-7-13-8)9-4-2-3-5-11(9)14-12/h2-7,14H,1H3 | StdInChIKey = PSFDQSOCUJVVGF-UHFFFAOYSA-N | RTECS = | MeSHName = | ChEBI = 5623 | KEGG = C09209}} |Section2={{Chembox Properties | C=12 | H=10 | N=2 | Appearance = | Density = | MeltingPtC = 235-238 | BoilingPt = | Solubility = Soluble to 10 mM in 1 eq. HCl methanol: soluble 50 mg/ml}} |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}

'''Harmane''', or '''harman''', also known as '''1-methyl-β-carboline''', is a heterocyclic amine and β-carboline found in a variety of foods including coffee,<ref name=pmid16139309 >{{cite journal | pmid = 16139309 | year = 2006 | last1 = Herraiz | first1 = T | title = Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee | journal = Life Sciences | volume = 78 | issue = 8 | pages = 795–802 | last2 = Chaparro | first2 = C | doi = 10.1016/j.lfs.2005.05.074 }}</ref> sauces,<ref>{{Cite journal | doi = 10.1080/02652030400019844| pmid = 15764332| title = Relative exposure toβ-carbolines norharman and harman from foods and tobacco smoke| journal = Food Additives and Contaminants| volume = 21| issue = 11| pages = 1041–50| year = 2004| last1 = Herraiz | first1 = T.| bibcode = 2004FACon..21.1041H| s2cid = 216644379}}</ref> and cooked meat.<ref name="ReferenceA">{{cite journal | pmid = 17497412 | pmc = 4993204 | year = 2007 | last1 = Louis | first1 = E. D. | title = Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness | journal = Journal of Toxicology and Environmental Health, Part A | volume = 70 | issue = 12 | pages = 1014–9 | last2 = Zheng | first2 = W | last3 = Jiang | first3 = W | last4 = Bogen | first4 = K. T. | last5 = Keating | first5 = G. A. | doi = 10.1080/15287390601172015 | bibcode = 2007JTEHA..70.1014L }}</ref> It is also present in tobacco smoke.<ref>{{cite journal | doi = 10.1016/j.bbrc.2004.11.033| pmid = 15582589| title = Human monoamine oxidase is inhibited by tobacco smoke: β-carboline alkaloids act as potent and reversible inhibitors| journal = Biochemical and Biophysical Research Communications| volume = 326| issue = 2| pages = 378–86| year = 2005| last1 = Herraiz| first1 = Tomas| last2 = Chaparro| first2 = Carolina| bibcode = 2005BBRC..326..378H}}</ref>

Harmane is related to other alkaloids, harmine and harmaline, found in 1837 in the plant ''Peganum harmala''.<ref>{{cite web |last1=Claude Lotfi |title=Contribution à l'étude du Peganum harmala (L.) (Hermel) |url=http://chimie.these.free.fr/CHIMTHE%20056.htm |date=1967}}</ref> The name derives from the Arabic word for the plant, {{Lang|ar|حَرْمَل|rtl=yes}} ({{Lang|ar-latn|ḥarmal}}).

In humans, harmane is a potent tremor-producing neurotoxin.<ref>{{Cite journal|last1=Louis|first1=Elan D|last2=Jiang|first2=Wendy|last3=Pellegrino |first3=Kathryn M|last4=Rios|first4=Eileen|last5=Factor-Litvak|first5=Pam|last6=Henchcliffe |first6=Claire|last7=Zheng|first7=Wei|date=2008|title=Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor|journal=Neurotoxicology|volume=29|issue=2|pages=294–300|doi=10.1016/j.neuro.2007.12.001|pmid=18242711|pmc=2291546 |bibcode=2008NeuTx..29..294L }}</ref> Harmane has been found to inhibit the early stages of the growth of the malaria parasite in the gut of mosquitoes infected by the bacterium ''Delftia tsuruhatensis'', and can be absorbed by the mosquitoes upon contact.<ref>{{Cite journal |last1=Huang |first1=Wei |last2=Rodrigues |first2=Janneth |last3=Bilgo |first3=Etienne |last4=Tormo |first4=José R. |last5=Challenger |first5=Joseph D. |last6=De Cozar-Gallardo |first6=Cristina |last7=Pérez-Victoria |first7=Ignacio |last8=Reyes |first8=Fernando |last9=Castañeda-Casado |first9=Pablo |last10=Gnambani |first10=Edounou Jacques |last11=Hien |first11=Domonbabele François de Sales |last12=Konkobo |first12=Maurice |last13=Urones |first13=Beatriz |last14=Coppens |first14=Isabelle |last15=Mendoza-Losana |first15=Alfonso |date=2023-08-04 |title=Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes |url=https://www.science.org/doi/10.1126/science.adf8141 |journal=Science |language=en |volume=381 |issue=6657 |pages=533–540 |doi=10.1126/science.adf8141 |pmid=37535741 |bibcode=2023Sci...381..533H |issn=0036-8075|hdl=10044/1/105278 |s2cid=260440907 |hdl-access=free }}</ref><ref>{{Cite news |last=Offord |first=Catherine |date=3 August 2023 |title=Microbe stops mosquitoes from harboring malaria parasite |work=Science |url=https://www.science.org/content/article/microbe-stops-mosquitoes-harboring-malaria-parasite}}</ref><ref>{{cite web |last1=Naomi Grimley |title=Chance discovery helps fight against malaria |url=https://www.bbc.com/news/health-66394117 |publisher=BBC |date=Aug 4, 2023}}</ref>

==Pharmacology== ===Pharmacodynamics=== Harmane is a potent reversible inhibitor of monoamine oxidase A (RIMA), with an {{Abbrlink|IC50|half-maximal inhibitory concentration}} of 60{{nbsp}}nM.<ref name="SaroJohneLatino2025">{{cite journal | vauthors = Saro G, Johne S, Latino DA, Moine F, van der Toorn M, Mathis C, Veljkovic E | title = Monoamine Oxidase Inhibitors Present in Tobacco Modulate Dopamine Balance Via the Dopamine Transporter | journal = ACS Chem Neurosci | volume = 16 | issue = 6 | pages = 1117–1131 | date = March 2025 | pmid = 40033845 | pmc = 11926787 | doi = 10.1021/acschemneuro.4c00789 | url = }}</ref> It is also a weak dopamine reuptake inhibitor (DRI), with an {{Abbr|IC50|half-maximal inhibitory concentration}} of 1,490{{nbsp}}nM at the dopamine transporter (DAT).<ref name="SaroJohneLatino2025" />

Harmane shows weak affinity for the serotonin 5-HT2B and 5-HT2C receptors (Ki = 267{{nbsp}}nM and 1,135{{nbsp}}nM, respectively), but not for the serotonin 5-HT2A receptor (Ki = >10,000{{nbsp}}nM).<ref name="FoleyAl-IssaHiller2019">{{cite journal | last1=Foley | first1=Caroline A. | last2=Al-Issa | first2=Yazan A. | last3=Hiller | first3=Kathryn P. | last4=Mulcahy | first4=Seann P. | title=Synthesis and Structure–Activity Relationships of 1-Aryl-β-carbolines as Affinity Probes for the 5-Hydroxytryptamine Receptor | journal=ACS Omega | volume=4 | issue=6 | date=30 June 2019 | issn=2470-1343 | doi=10.1021/acsomega.9b01111 | pages=9807–9812 | doi-access=free }}</ref> It has been found to be inactive as an agonist of the serotonin 5-HT2A receptor.<ref name="RabinReginaDoat2002">{{cite journal | vauthors = Rabin RA, Regina M, Doat M, Winter JC | title = 5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens | journal = Pharmacol Biochem Behav | volume = 72 | issue = 1–2 | pages = 29–37 | date = May 2002 | pmid = 11900766 | doi = 10.1016/s0091-3057(01)00720-1 | url = }}</ref>

Harmane fails to substitute for the psychedelic drug 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> This is similar to the case of harmine but is in contrast to harmaline and 6-methoxyharmalan.<ref name="GlennonYoungJacyno1983" />

==Chemistry== Harmane is a methylated derivative of β-carboline with the molecular formula C12H10N2.

==Natural occurrence== {| class="wikitable sortable" |+ Plant sources |- ! Family !! Plant |- | Rubiaceae || ''Coffea arabica''<ref name="pmid16139309" /> |- | Solanaceae || ''Nicotiana tabacum''<ref name="Poindexter">{{cite journal | last1=Poindexter | first1=E.H. | last2=Carpenter | first2=R.D. | title=The isolation of harmane and norharmane from tobacco and cigarette smoke | journal=Phytochemistry | volume=1 | issue=3 | year=1962 | issn=0031-9422 | doi=10.1016/s0031-9422(00)82825-3 | pages=215–221| bibcode=1962PChem...1..215P }}</ref> |- | Theaceae || ''Camellia sinensis''<ref>{{Cite journal|last1=Jiao|first1=Ye|last2=Yan|first2=Yan|last3=He|first3=Zhiyong|last4=Gao|first4=Daming|last5=Qin|first5=Fang|last6=Lu|first6=Mei|last7=Xie|first7=Mingyong|last8=Chen|first8=Jie|last9=Zeng|first9=Maomao|date=2018-06-20|title=Inhibitory effects of catechins on β-carbolines in tea leaves and chemical model systems|journal=Food & Function|volume=9|issue=6|pages=3126–3133|doi=10.1039/c7fo02053h|issn=2042-650X|pmid=29789822}}</ref> |}

In 1962, Poindexter ''et al.'' found that there was very little harmane in tobacco, but a significant amount in tobacco smoke. They showed that it is produced from tryptophan by the heat of burning the tobacco.<ref name="Poindexter"/>

==Society and culture== ===Legal status=== ====Canada==== Harmane is not a controlled substance in Canada as of 2025.<ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

== See also == * Substituted β-carboline * Harmine

== References == {{Reflist}}

==External links== * [https://isomerdesign.com/pihkal/explore/5402 Harman - Isomer Design]

Category:Beta-Carbolines Category:Dopamine reuptake inhibitors Category:Malaria Category:Monoamine oxidase inhibitors