Wikipedia

Harmane

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,[1] sauces,[2] and cooked meat.[3] It is also present in tobacco smoke.[4]

Harmane
Names
Preferred IUPAC name
1-Methyl-9H-pyrido[3,4-b]indole
Other names
Harman, 1-Methyl-β-carboline, Aribine, Aribin, Locuturine, Locuturin, Loturine, Passiflorin, 1-Methylnorharman, NSC 54439
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.006.948 Edit this at Wikidata
EC Number
  • 207-642-2
KEGG
UNII
  • InChI=1S/C12H10N2/c1-8-12-10(6-7-13-8)9-4-2-3-5-11(9)14-12/h2-7,14H,1H3
    Key: PSFDQSOCUJVVGF-UHFFFAOYSA-N
  • InChI=1/C12H10N2/c1-8-12-10(6-7-13-8)9-4-2-3-5-11(9)14-12/h2-7,14H,1H3
    Key: PSFDQSOCUJVVGF-UHFFFAOYAA
  • CC1=NC=CC2=C1NC3=CC=CC=C23
Properties
C12H10N2
Molar mass 182.226 g·mol−1
Melting point 235–238 °C (455–460 °F; 508–511 K)
Soluble to 10 mM in 1 eq. HCl

methanol: soluble 50 mg/ml

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Harmane is related to other alkaloids, harmine and harmaline, found in 1837 in the plant Peganum harmala.[5] The name derives from the Arabic word for the plant, حَرْمَل (ḥarmal).

In humans, harmane is a potent tremor-producing neurotoxin.[6] 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.[7][8][9]

Pharmacology

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Pharmacodynamics

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Harmane is a potent reversible inhibitor of monoamine oxidase A (RIMA), with an IC50Tooltip half-maximal inhibitory concentration of 60 nM.[10] It is also a weak dopamine reuptake inhibitor (DRI), with an IC50 of 1,490 nM at the dopamine transporter (DAT).[10]

Harmane shows weak affinity for the serotonin 5-HT2B and 5-HT2C receptors (Ki = 267 nM and 1,135 nM, respectively), but not for the serotonin 5-HT2A receptor (Ki = >10,000 nM).[11] It has been found to be inactive as an agonist of the serotonin 5-HT2A receptor.[12]

Harmane fails to substitute for the psychedelic drug DOM in rodent drug discrimination tests.[13] This is similar to the case of harmine but is in contrast to harmaline and 6-methoxyharmalan.[13]

Chemistry

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

Natural occurrence

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Plant sources
FamilyPlant
RubiaceaeCoffea arabica[1]
SolanaceaeNicotiana tabacum[14]
TheaceaeCamellia sinensis[15]

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.[14]

Society and culture

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Canada

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Harmane is not a controlled substance in Canada as of 2025.[16]

See also

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References

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  1. 1 2 Herraiz, T; Chaparro, C (2006). "Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee". Life Sciences. 78 (8): 795–802. doi:10.1016/j.lfs.2005.05.074. PMID 16139309.
  2. ↑ Herraiz, T. (2004). "Relative exposure toβ-carbolines norharman and harman from foods and tobacco smoke". Food Additives and Contaminants. 21 (11): 1041–50. Bibcode:2004FACon..21.1041H. doi:10.1080/02652030400019844. PMID 15764332. S2CID 216644379.
  3. ↑ Louis, E. D.; Zheng, W; Jiang, W; Bogen, K. T.; Keating, G. A. (2007). "Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness". Journal of Toxicology and Environmental Health, Part A. 70 (12): 1014–9. Bibcode:2007JTEHA..70.1014L. doi:10.1080/15287390601172015. PMC 4993204. PMID 17497412.
  4. ↑ Herraiz, Tomas; Chaparro, Carolina (2005). "Human monoamine oxidase is inhibited by tobacco smoke: β-carboline alkaloids act as potent and reversible inhibitors". Biochemical and Biophysical Research Communications. 326 (2): 378–86. Bibcode:2005BBRC..326..378H. doi:10.1016/j.bbrc.2004.11.033. PMID 15582589.
  5. ↑ Claude Lotfi (1967). "Contribution à l'étude du Peganum harmala (L.) (Hermel)".
  6. ↑ Louis, Elan D; Jiang, Wendy; Pellegrino, Kathryn M; Rios, Eileen; Factor-Litvak, Pam; Henchcliffe, Claire; Zheng, Wei (2008). "Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor". Neurotoxicology. 29 (2): 294–300. Bibcode:2008NeuTx..29..294L. doi:10.1016/j.neuro.2007.12.001. PMC 2291546. PMID 18242711.
  7. ↑ Huang, Wei; Rodrigues, Janneth; Bilgo, Etienne; Tormo, José R.; Challenger, Joseph D.; De Cozar-Gallardo, Cristina; Pérez-Victoria, Ignacio; Reyes, Fernando; Castañeda-Casado, Pablo; Gnambani, Edounou Jacques; Hien, Domonbabele François de Sales; Konkobo, Maurice; Urones, Beatriz; Coppens, Isabelle; Mendoza-Losana, Alfonso (2023-08-04). "Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes". Science. 381 (6657): 533–540. Bibcode:2023Sci...381..533H. doi:10.1126/science.adf8141. hdl:10044/1/105278. ISSN 0036-8075. PMID 37535741. S2CID 260440907.
  8. ↑ Offord, Catherine (3 August 2023). "Microbe stops mosquitoes from harboring malaria parasite". Science.
  9. ↑ Naomi Grimley (Aug 4, 2023). "Chance discovery helps fight against malaria". BBC.
  10. 1 2 Saro G, Johne S, Latino DA, Moine F, van der Toorn M, Mathis C, Veljkovic E (March 2025). "Monoamine Oxidase Inhibitors Present in Tobacco Modulate Dopamine Balance Via the Dopamine Transporter". ACS Chem Neurosci. 16 (6): 1117–1131. doi:10.1021/acschemneuro.4c00789. PMC 11926787. PMID 40033845.
  11. ↑ Foley, Caroline A.; Al-Issa, Yazan A.; Hiller, Kathryn P.; Mulcahy, Seann P. (30 June 2019). "Synthesis and Structure–Activity Relationships of 1-Aryl-β-carbolines as Affinity Probes for the 5-Hydroxytryptamine Receptor". ACS Omega. 4 (6): 9807–9812. doi:10.1021/acsomega.9b01111. ISSN 2470-1343.
  12. ↑ Rabin RA, Regina M, Doat M, Winter JC (May 2002). "5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens". Pharmacol Biochem Behav. 72 (1–2): 29–37. doi:10.1016/s0091-3057(01)00720-1. PMID 11900766.
  13. 1 2 Glennon RA, Young R, Jacyno JM, Slusher M, Rosecrans JA (January 1983). "DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines". Eur J Pharmacol. 86 (3–4): 453–459. doi:10.1016/0014-2999(83)90196-6. PMID 6572591.
  14. 1 2 Poindexter, E.H.; Carpenter, R.D. (1962). "The isolation of harmane and norharmane from tobacco and cigarette smoke". Phytochemistry. 1 (3): 215–221. Bibcode:1962PChem...1..215P. doi:10.1016/s0031-9422(00)82825-3. ISSN 0031-9422.
  15. ↑ Jiao, Ye; Yan, Yan; He, Zhiyong; Gao, Daming; Qin, Fang; Lu, Mei; Xie, Mingyong; Chen, Jie; Zeng, Maomao (2018-06-20). "Inhibitory effects of catechins on β-carbolines in tea leaves and chemical model systems". Food & Function. 9 (6): 3126–3133. doi:10.1039/c7fo02053h. ISSN 2042-650X. PMID 29789822.
  16. ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.
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