Chemistry:Harmane

From HandWiki

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

Pharmacodynamics

Harmane is a potent reversible inhibitor of monoamine oxidase A (RIMA), with an IC50 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

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

Natural occurrence

Plant sources
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

Canada

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

See also

References

  1. ↑ 1.0 1.1 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. doi:10.1080/02652030400019844. PMID 15764332. Bibcode: 2004FACon..21.1041H. 
  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. doi:10.1080/15287390601172015. PMID 17497412. Bibcode: 2007JTEHA..70.1014L. 
  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. doi:10.1016/j.bbrc.2004.11.033. PMID 15582589. Bibcode: 2005BBRC..326..378H. 
  5. ↑ Claude Lotfi (1967). "Contribution à l'étude du Peganum harmala (L.) (Hermel)". http://chimie.these.free.fr/CHIMTHE%20056.htm. 
  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-bindole) concentrations in essential tremor"]. Neurotoxicology 29 (2): 294–300. doi:10.1016/j.neuro.2007.12.001. PMID 18242711. Bibcode: 2008NeuTx..29..294L. 
  7. ↑ Huang, Wei; Rodrigues, Janneth; Bilgo, Etienne; Tormo, José R.; Challenger, Joseph D.; De Cozar-Gallardo, Cristina; Pérez-Victoria, Ignacio; Reyes, Fernando et al. (2023-08-04). "Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes" (in en). Science 381 (6657): 533–540. doi:10.1126/science.adf8141. ISSN 0036-8075. PMID 37535741. Bibcode: 2023Sci...381..533H. https://www.science.org/doi/10.1126/science.adf8141. 
  8. ↑ Offord, Catherine (3 August 2023). "Microbe stops mosquitoes from harboring malaria parasite". Science. https://www.science.org/content/article/microbe-stops-mosquitoes-harboring-malaria-parasite. 
  9. ↑ Naomi Grimley (Aug 4, 2023). "Chance discovery helps fight against malaria". BBC. https://www.bbc.com/news/health-66394117. 
  10. ↑ 10.0 10.1 "Monoamine Oxidase Inhibitors Present in Tobacco Modulate Dopamine Balance Via the Dopamine Transporter". ACS Chem Neurosci 16 (6): 1117–1131. March 2025. doi:10.1021/acschemneuro.4c00789. 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. ↑ "5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens". Pharmacol Biochem Behav 72 (1–2): 29–37. May 2002. doi:10.1016/s0091-3057(01)00720-1. PMID 11900766. 
  13. ↑ 13.0 13.1 "DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines". Eur J Pharmacol 86 (3–4): 453–459. January 1983. doi:10.1016/0014-2999(83)90196-6. PMID 6572591. 
  14. ↑ 14.0 14.1 Poindexter, E.H.; Carpenter, R.D. (1962). "The isolation of harmane and norharmane from tobacco and cigarette smoke". Phytochemistry 1 (3): 215–221. doi:10.1016/s0031-9422(00)82825-3. ISSN 0031-9422. Bibcode: 1962PChem...1..215P. 
  15. ↑ Jiao, Ye; Yan, Yan; He, Zhiyong; Gao, Daming; Qin, Fang; Lu, Mei; Xie, Mingyong; Chen, Jie et al. (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". https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html. 



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