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) |
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| ChEBI | |
| ChemSpider | |
| ECHA InfoCard | 100.006.948 Edit this at Wikidata |
| EC Number |
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| KEGG | |
PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C12H10N2 | |
| Molar mass | 182.226g·mol−1 |
| Melting point | 235–238°C (455–460°F; 508–511K) |
| 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], 100kPa).
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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 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
[edit ]Pharmacodynamics
[edit ]Harmane is a potent reversible inhibitor of monoamine oxidase A (RIMA), with an IC50 Tooltip half-maximal inhibitory concentration of 60nM.[10] It is also a weak dopamine reuptake inhibitor (DRI), with an IC50 of 1,490nM at the dopamine transporter (DAT).[10]
Harmane shows weak affinity for the serotonin 5-HT2B and 5-HT2C receptors (Ki = 267nM and 1,135nM, respectively), but not for the serotonin 5-HT2A receptor (Ki =>10,000nM).[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
[edit ]Harmane is a methylated derivative of β-carboline with the molecular formula C12H10N2.
Natural occurrence
[edit ]| Family | Plant |
|---|---|
| Rubiaceae | Coffea arabica [1] |
| Solanaceae | Nicotiana tabacum [14] |
| Theaceae | Camellia 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
[edit ]Legal status
[edit ]Canada
[edit ]Harmane is not a controlled substance in Canada as of 2025.[16]
See also
[edit ]References
[edit ]- 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年05月07日4. PMID 16139309.
- ↑ 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.
- ↑ 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.
- ↑ 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年11月03日3. PMID 15582589.
- ↑ Claude Lotfi (1967). "Contribution à l'étude du Peganum harmala (L.) (Hermel)".
- ↑ 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.200712001. PMC 2291546 . PMID 18242711.
- ↑ 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年08月04日). "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.
- ↑ Offord, Catherine (3 August 2023). "Microbe stops mosquitoes from harboring malaria parasite". Science .
- ↑ Naomi Grimley (Aug 4, 2023). "Chance discovery helps fight against malaria". BBC.
- 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.
- ↑ 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.
- ↑ 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.
- 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.
- 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.
- ↑ Jiao, Ye; Yan, Yan; He, Zhiyong; Gao, Daming; Qin, Fang; Lu, Mei; Xie, Mingyong; Chen, Jie; Zeng, Maomao (2018年06月20日). "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.
- ↑ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.