Β-Carboline: Difference between revisions

{{short description|Chemical compound also known as norharmane}}

{{cs1 config|name-list-style=vanc}}

{{DISPLAYTITLE:β-Carboline}}

| verifiedrevid = 443419704

| ImageFile=beta-Carboline.svg

| ImageFile2=Β-Carboline.png

| ImageAlt2=Chemical structure of β-carboline

| PIN=9''H''-Pyrido[3,4-''b'']indole

| OtherNames={{ubl|Norharmane|Norharman|9''H''-β-Carboline}}

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 8222

| InChIKey = AIFRHYZBTHREPW-UHFFFAOYAG

| Beilstein = 128414

| EC_number = 205-959-0

| KEGG = C20157

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 94HMA1I78O

| PubChem=64961

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 109895

| SMILES=c1ccc3c(c1)[nH]c2cnccc23

| InChI=1/C11H8N2/c1-2-4-10-8(3-1)9-5-6-12-7-11(9)13-10/h1-7,13H

| MeSHName=norharman

}}

|Section2={{Chembox Properties

| Formula=C₁₁H₈N₂

| MolarMass=168.20 g/mol

}}

'''β-Carboline''' (9''H''-[[Pyridine|pyrido]][3,4-''b''][[indole]]) represents the basic chemical structure for more than one hundred [[alkaloid]]s and synthetic compounds. The effects of these substances depend on their respective [[substituent]]. Natural β-carbolines primarily influence [[brain functions]] but can also exhibit [[antioxidant]]<ref>{{cite journal | vauthors = Francik R, Kazek G, Cegła M, Stepniewski M | title = Antioxidant activity of beta-carboline derivatives | journal = Acta Poloniae Pharmaceutica | volume = 68 | issue = 2 | pages = 185–189 | date = March 2011 | pmid = 21485291 }}</ref> effects. Synthetically designed β-carboline [[Derivative (chemistry)|derivatives]] have recently been shown to have [[Neuroprotection|neuroprotective]],<ref>{{cite journal | vauthors = Gulyaeva N, Aniol V | title = Good guys from a shady family | journal = Journal of Neurochemistry | volume = 121 | issue = 6 | pages = 841–842 | date = June 2012 | pmid = 22372749 | doi = 10.1111/j.1471-4159.2012.07708.x | s2cid = 205624339 | doi-access = free }}</ref> [[Neuroenhancement|cognitive enhancing]] and anti-[[cancer]] properties.<ref name="β-Carbolines as potential anticance">{{cite journal | vauthors = Aaghaz S, Sharma K, Jain R, Kamal A | title = β-Carbolines as potential anticancer agents | journal = European Journal of Medicinal Chemistry | volume = 216 | pages = 113321 | date = April 2021 | pmid = 33684825 | doi = 10.1016/j.ejmech.2021.113321 | s2cid = 232159513 }}</ref>

The pharmacological effects of specific β-carbolines are dependent on their [[substituent]]s. For example, the natural β-carboline [[harmine]] has substituents on position 7 and 1. Thereby, it acts as a selective [[Enzyme inhibitor|inhibitor]] of the [[DYRK1A]] [[protein kinase]], a molecule necessary for [[neurodevelopment]].<ref>{{cite journal | vauthors = Mennenga SE, Gerson JE, Dunckley T, Bimonte-Nelson HA | title = Harmine treatment enhances short-term memory in old rats: Dissociation of cognition and the ability to perform the procedural requirements of maze testing | journal = Physiology & Behavior | volume = 138 | pages = 260–265 | date = January 2015 | pmid = 25250831 | pmc = 4406242 | doi = 10.1016/j.physbeh.2014.09.001 }}</ref><ref>{{cite journal | vauthors = Becker W, Sippl W | title = Activation, regulation, and inhibition of DYRK1A | journal = The FEBS Journal | volume = 278 | issue = 2 | pages = 246–256 | date = January 2011 | pmid = 21126318 | doi = 10.1111/j.1742-4658.2010.07956.x | s2cid = 27837814 | doi-access = free }}</ref> It also exhibits various [[antidepressant]]-like effects in rats by interacting with [[Serotonin 2A receptor|serotonin receptor 2A]].<ref>{{cite journal | vauthors = Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV | display-authors = 6 | title = Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors | journal = Drug and Alcohol Dependence | volume = 60 | issue = 2 | pages = 121–132 | date = August 2000 | pmid = 10940539 | doi = 10.1016/s0376-8716(99)00148-9 }}</ref><ref name=":2">{{cite journal | vauthors = Fortunato JJ, Réus GZ, Kirsch TR, Stringari RB, Stertz L, Kapczinski F, Pinto JP, Hallak JE, Zuardi AW, Crippa JA, Quevedo J | display-authors = 6 | title = Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 33 | issue = 8 | pages = 1425–1430 | date = November 2009 | pmid = 19632287 | doi = 10.1016/j.pnpbp.2009.07.021 | series = Bed nucleus of the stria terminalis: anatomy, physiology, functions | s2cid = 207408868 | doi-access = free }}</ref> Furthermore, it increases levels of the [[brain-derived neurotrophic factor]] ([[Brain-derived neurotrophic factor|BDNF]]) in rat [[hippocampus]].<ref name=":2" /><ref name=":3">{{cite journal | vauthors = Fortunato JJ, Réus GZ, Kirsch TR, Stringari RB, Fries GR, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J | display-authors = 6 | title = Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus | journal = Journal of Neural Transmission | volume = 117 | issue = 10 | pages = 1131–1137 | date = October 2010 | pmid = 20686906 | doi = 10.1007/s00702-010-0451-2 | s2cid = 21595062 }}</ref> A decreased BDNF level has been associated with major [[Depression (mood)|depression]] in humans. The antidepressant effect of harmine might also be due to its function as a [[Monoamine oxidase inhibitor|MAO-A inhibitor]] by reducing the breakdown of [[serotonin]] and [[noradrenaline]].<ref name=":3" /><ref>{{cite journal | vauthors = López-Muñoz F, Alamo C | title = Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today | journal = Current Pharmaceutical Design | volume = 15 | issue = 14 | pages = 1563–1586 | date = 2009-05-01 | pmid = 19442174 | doi = 10.2174/138161209788168001 }}</ref>

A synthetic [[Derivative (chemistry)|derivative]], [[9-Methyl-β-carboline|9-methyl-β-carboline]], has shown [[Neuroprotection|neuroprotective]] effects including increased [[Gene expression|expression]] of [[neurotrophic factors]] and enhanced [[respiratory chain]] activity.<ref>{{Cite book|date=2012| veditors = Antkiewicz-Michaluk L, Rommelspacher H |title=Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants |language=en-gb|doi=10.1007/978-1-4614-1542-8| isbn = 978-1-4614-1541-1 | s2cid = 28551023 }}</ref><ref name=":4">{{cite journal | vauthors = Wernicke C, Hellmann J, Zieba B, Kuter K, Ossowska K, Frenzel M, Dencher NA, Rommelspacher H | display-authors = 6 | title = 9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease | journal = Pharmacological Reports | volume = 62 | issue = 1 | pages = 35–53 | date = January 2010 | pmid = 20360614 | doi = 10.1016/s1734-1140(10)70241-3 | s2cid = 16729205 }}</ref> This derivative has also been shown to enhance [[cognitive function]],<ref name="9-Methyl-β-carboline-induced cognit">{{cite journal | vauthors = Gruss M, Appenroth D, Flubacher A, Enzensperger C, Bock J, Fleck C, Gille G, Braun K | display-authors = 6 | title = 9-Methyl-β-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation | journal = Journal of Neurochemistry | volume = 121 | issue = 6 | pages = 924–931 | date = June 2012 | pmid = 22380576 | doi = 10.1111/j.1471-4159.2012.07713.x | s2cid = 8832937 | doi-access = free }}</ref> increase [[dopaminergic]] neuron count and facilitate [[Synapse|synaptic]] and [[Dendrite|dendritic]] proliferation.<ref>{{cite journal | vauthors = Hamann J, Wernicke C, Lehmann J, Reichmann H, Rommelspacher H, Gille G | title = 9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture | journal = Neurochemistry International | volume = 52 | issue = 4–5 | pages = 688–700 | date = March 2008 | pmid = 17913302 | doi = 10.1016/j.neuint.2007.08.018 | s2cid = 24226033 }}</ref><ref>{{cite journal | vauthors = Polanski W, Reichmann H, Gille G | title = Stimulation, protection and regeneration of dopaminergic neurons by 9-methyl-β-carboline: a new anti-Parkinson drug? | journal = Expert Review of Neurotherapeutics | volume = 11 | issue = 6 | pages = 845–860 | date = June 2011 | pmid = 21651332 | doi = 10.1586/ern.11.1 | s2cid = 24899640 }}</ref> It also exhibited therapeutic effects in animal models for [[Parkinson's disease]] and other [[Neurodegeneration|neurodegenerative]] processes.<ref name=":4" />

However, β-carbolines with substituents in position 3 reduce the effect of [[benzodiazepine]] on [[GABAA receptor|GABA-A receptors]] and can therefore have [[Convulsion|convulsive]], [[anxiogenic]] and memory enhancing effects.<ref name=":0">{{cite journal | vauthors = Venault P, Chapouthier G | title = From the behavioral pharmacology of beta-carbolines to seizures, anxiety, and memory | journal = TheScientificWorldJournal | volume = 7 | pages = 204–223 | date = February 2007 | pmid = 17334612 | pmc = 5901106 | doi = 10.1100/tsw.2007.48 | doi-access = free }}</ref> Moreover, 3-hydroxymethyl-beta-carboline blocks the sleep-promoting effect of [[flurazepam]] in rodents and - by itself - can decrease sleep in a dose-dependent manner.<ref name=":1">{{cite journal | vauthors = Mendelson WB, Cain M, Cook JM, Paul SM, Skolnick P | title = A benzodiazepine receptor antagonist decreases sleep and reverses the hypnotic actions of flurazepam | journal = Science | volume = 219 | issue = 4583 | pages = 414–416 | date = January 1983 | pmid = 6294835 | doi = 10.1126/science.6294835 | bibcode = 1983Sci...219..414M | s2cid = 43038332 }}</ref> Another derivative, methyl-β-carboline-3-carboxylate, stimulates learning and memory at low [[Dose (biochemistry)|doses]] but can promote anxiety and convulsions at high doses.<ref name=":0"/> With modification in position 9 similar positive effects have been observed for learning and memory without promotion of anxiety or convulsion.<ref name="9-Methyl-β-carboline-induced cognit"/>

β-carboline derivatives also enhance the production of the [[antibiotic]] reveromycin A in soil dwelling "[[Streptomyces]]" species.<ref>{{cite journal|vauthors=Panthee S, Takahashi S, Hayashi T, Shimizu T, Osada H|date=April 2019|title=β-carboline biomediators induce reveromycin production in Streptomyces sp. SN-593|journal=Scientific Reports|volume=9|issue=1|pages=5802|bibcode=2019NatSR...9.5802P|doi=10.1038/s41598-019-42268-w|pmc=6456619|pmid=30967594|doi-access=free}}</ref><ref>{{cite journal|display-authors=6|vauthors=Panthee S, Kito N, Hayashi T, Shimizu T, Ishikawa J, Hamamoto H, Osada H, Takahashi S|date=June 2020|title=β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593|journal=Scientific Reports|volume=10|issue=1|pages=10230|bibcode=2020NatSR..1010230P|doi=10.1038/s41598-020-66974-y|pmc=7311520|pmid=32576869|doi-access=free}}</ref> Specifically, expression of [[Biosynthesis|biosynthetic]] [[gene]]s is facilitated by binding of the β-carboline to a large [[Adenosine triphosphate|ATP]]-binding regulator of the [[LuxR-type DNA-binding HTH domain|LuxR]] family.

Also [[Lactobacillus|Lactobacillus spp.]] secretes a β-carboline (1-acetyl-β-carboline) preventing the pathogenic fungus [[Candida albicans]] to change to a more [[Virulence|virulent]] growth form (yeast-to-filament transition). Thereby, β-carboline reverses imbalances in the [[microbiome]] composition causing [[Pathology|pathologies]] ranging from [[Vaginal yeast infection|vaginal candidiasis]] to fungal sepsis.<ref>{{cite journal|display-authors=6|vauthors=MacAlpine J, Daniel-Ivad M, Liu Z, Yano J, Revie NM, Todd RT, Stogios PJ, Sanchez H, O'Meara TR, Tompkins TA, Savchenko A, Selmecki A, Veri AO, Andes DR, Fidel PL, Robbins N, Nodwell J, Whitesell L, Cowen LE|date=October 2021|title=A small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase|journal=Nature Communications|volume=12|issue=1|pages=6151|doi=10.1038/s41467-021-26390-w|pmid=34686660|pmc=8536679 |bibcode=2021NatCo..12.6151M }}</ref>

Since β-carbolines also interact with various [[cancer]]-related molecules such as [[DNA]], [[enzyme]]s ([[GPX4]], [[kinase]]s, etc.) and [[protein]]s ([[ABCG2]]/BRCP1, etc.), they are also discussed as potential anticancer agents.<ref name="β-Carbolines as potential anticance" />

=== Explorative human studies for the medical use of β-carbolines ===

The extract of the [[liana]] [[Banisteriopsis caapi]] has been used by the tribes of the [[Amazon rainforest|Amazon]] as an [[entheogen]] and was described as a [[hallucinogen]] in the middle of the 19th century.<ref name=":5">{{cite journal | vauthors = Djamshidian A, Bernschneider-Reif S, Poewe W, Lees AJ | title = ''Banisteriopsis caapi'', a Forgotten Potential Therapy for Parkinson's Disease? | journal = Movement Disorders Clinical Practice | volume = 3 | issue = 1 | pages = 19–26 | date = 2016 | pmid = 30713897 | pmc = 6353393 | doi = 10.1002/mdc3.12242 }}</ref> In early 20th century, European pharmacists identified [[harmine]] as the active substance.<ref>{{cite journal | vauthors = Foley P | title = Beans, roots and leaves: a brief history of the pharmacological therapy of parkinsonism | journal = Wurzburger Medizinhistorische Mitteilungen | volume = 22 | pages = 215–234 | date = 2003 | pmid = 15641199 }}</ref> This discovery stimulated the interest to further investigate its potential as a medicine. For example, [[Louis Lewin]], a prominent pharmacologist, demonstrated a dramatic benefit in neurological impairments after injections of ''B. caapi'' in patients with [[Postencephalitic parkinsonism|postencephalitic Parkinsonism]].<ref name=":5" /> By 1930, it was generally agreed that [[hypokinesia]], [[drooling]], mood, and sometimes rigidity improved by treatment with harmine. Altogether, 25 studies had been published in the 1920s and 1930s about patients with [[Parkinson's disease]] and postencephalitic Parkinsonism. The pharmacological effects of harmine have been attributed mainly to its central [[monoamine oxidase]] (MAO) inhibitory properties. [[In vivo|In-vivo]] and rodent studies have shown that extracts of ''Banisteriopsis caapi'' and also ''[[Peganum harmala]]'' lead to [[Striatum|striatal]] [[dopamine]] release.<ref>{{cite journal | vauthors = Schwarz MJ, Houghton PJ, Rose S, Jenner P, Lees AD | title = Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism | journal = Pharmacology, Biochemistry, and Behavior | volume = 75 | issue = 3 | pages = 627–633 | date = June 2003 | pmid = 12895680 | doi = 10.1016/s0091-3057(03)00129-1 | s2cid = 28243440 }}</ref><ref>{{cite journal | vauthors = Brierley DI, Davidson C | title = Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell | journal = Journal of Psychopharmacology | volume = 27 | issue = 1 | pages = 98–108 | date = January 2013 | pmid = 23076833 | doi = 10.1177/0269881112463125 | s2cid = 40115950 }}</ref><ref>{{cite journal | vauthors = Samoylenko V, Rahman MM, Tekwani BL, Tripathi LM, Wang YH, Khan SI, Khan IA, Miller LS, Joshi VC, Muhammad I | display-authors = 6 | title = Banisteriopsis caapi, a unique combination of MAO inhibitory and antioxidative constituents for the activities relevant to neurodegenerative disorders and Parkinson's disease | journal = Journal of Ethnopharmacology | volume = 127 | issue = 2 | pages = 357–367 | date = February 2010 | pmid = 19879939 | pmc=2828149| doi = 10.1016/j.jep.2009.10.030 }}</ref> Furthermore, harmine supports the survival of dopaminergic neurons in [[MPTP]]-treated mice.<ref>{{cite journal | vauthors = Barallobre MJ, Perier C, Bové J, Laguna A, Delabar JM, Vila M, Arbonés ML | title = DYRK1A promotes dopaminergic neuron survival in the developing brain and in a mouse model of Parkinson's disease | journal = Cell Death & Disease | volume = 5 | issue = 6 | pages = e1289 | date = June 2014 | pmid = 24922073 | doi = 10.1038/cddis.2014.253|pmc=4611726 }}</ref> Since harmine also [[Antagonist (drug)|antagonizes]] [[N-Methyl-D-aspartic acid|''N''-methyl-d-aspartate]] (NMDA) receptors,<ref>{{cite journal | vauthors = Du W, Aloyo VJ, Harvey JA | title = Harmaline competitively inhibits [3H]MK-801 binding to the NMDA receptor in rabbit brain | journal = Brain Research | volume = 770 | issue = 1–2 | pages = 26–29 | date = October 1997 | pmid = 9372198 | doi = 10.1016/s0006-8993(97)00606-9 | s2cid = 10309111 }}</ref> some researchers speculatively attributed the rapid improvement in patients with Parkinson's disease to these antiglutamatergic effects.<ref name=":5" /> However, the advent of synthetic [[anticholinergic]] drugs at that time led to the total abandonment of harmine.<ref name=":5" />

== Structure ==

β-Carbolines belong to the group of [[indole alkaloids]] and consist of [[pyridine|a pyridine]] ring that is fused to an [[indole]] skeleton.<ref>''The Encyclopedia of Psychoactive Plants: Ethnopharmacology and its Applications''. Ratsch, Christian. Park Street Press c. 2005</ref> The structure of β-carboline is similar to that of [[tryptamine]], with the [[ethylamine]] chain re-connected to the [[indole]] ring via an extra [[carbon]] atom, to produce a three-ringed structure. The biosynthesis of β-carbolines is believed to follow this route from analogous tryptamines.<ref>{{cite journal | vauthors = Baiget J, Llona-Minguez S, Lang S, Mackay SP, Suckling CJ, Sutcliffe OB | title = Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1-carboxylate: Concise synthesis of alangiobussinine | journal = Beilstein Journal of Organic Chemistry | volume = 7 | pages = 1407–1411 | year = 2011 | pmid = 22043251 | pmc = 3201054 | doi = 10.3762/bjoc.7.164 }}</ref> Different levels of [[Saturated and unsaturated compounds|saturation]] are possible in the third ring which is indicated here in the [[structural formula]] by coloring the optionally double bonds red and blue:

Some of the more important β-carbolines are tabulated by structure below. Their structures may contain the aforementioned bonds marked by red or blue.

{| class="wikitable" style="text-align: center;"

! scope="col" | Short Name

! scope="col" style="min-width: 5em;" | R1

! scope="col" style="min-width: 5em;" | R6

! scope="col" style="min-width: 5em;" | R7

! scope="col" style="min-width: 5em;" | R9

! scope="col" style="min-width: 5em;" | Structure

| style="text-align: left;" | β-Carboline || H || H || H || H || [[Image:Beta-Carboline.svg|β-Carboline|100px]]

| style="text-align: left;" | [[Pinoline]]|| H || [[Methoxy|OCH₃]]|| H || H || [[Image:Pinoline.svg|125px|Pinoline]]

| style="text-align: left;" | [[Harmane]]|| [[Methyl|CH₃]]|| H || H || H || [[Image:Harmane_structure.svg|100px|Harmane]]

| style="text-align: left;" | [[Harmine]]|| [[Methyl|CH₃]]|| H || [[Methoxy|OCH₃]]|| H || [[Image:Harmine structure.svg|125px|Harmine]]

| style="text-align: left;" | [[Harmaline]]|| [[Methyl|CH₃]]|| H || [[Methoxy|OCH₃]]|| H || [[Image:Harmaline structure.svg|125px|Harmaline]]

| style="text-align: left;" | [[Harmalol]]|| [[Methyl|CH₃]]|| H || [[Hydroxy group|OH]]|| H || [[Image:Harmalol structure.svg|125px|Harmalol]]

| style="text-align: left;" | [[Tetrahydroharmine]]|| [[Methyl|CH₃]]|| H || [[Methoxy|OCH₃]]|| H || [[Image:Tetrahydroharmine structure.svg|125px|Tetrahydroharmine]]

|-

| style="text-align: left;" | [[9-Methyl-β-carboline]]|| H || H || H || [[Methyl|CH₃]]|| [[Image:9-Me-BC_bkchem_autocropped.svg|125px|9-Me-BC]]

|-

|3-Carboxy-Tetrahydrononharman

|H / CH₃ / COOH

|H

|H

|H

|[[File:3-Carboxy-Tetrahydronorharman3.svg|153x153px]]

==Natural occurrence==

[[File:Arachnida,_Scorpiones,_Paruroctonus_scorpion_under_UV_(4818403697).jpg|thumb|300px|A [[Paruroctonus]] scorpion [[Fluorescence|fluorescing]] under a [[blacklight]]]]

β-Carboline [[alkaloid]]s are widespread in [[prokaryote]]s, [[plant]]s and [[animal]]s. Some β-carbolines, notably tetrahydro-β-carbolines, may be formed naturally in plants and the human body with [[tryptophan]], [[serotonin]] and [[tryptamine]] as [[Precursor (chemistry)|precursors]].

* Altogether, eight plant families are known to express 64 different kinds of β-carboline alkaloids. For example, the β-carbolines [[harmine]], [[harmaline]], and [[tetrahydroharmine]] are components of the liana ''[[Banisteriopsis caapi]]'' and play a pivotal role in the pharmacology of the indigenous [[psychedelic drug]] [[ayahuasca]]. Moreover, the seeds of ''[[Peganum harmala]]'' ([[Peganum harmala|Syrian Rue]]) contain between 0.16%<ref>{{cite journal | vauthors = Hemmateenejad B, Abbaspour A, Maghami H, Miri R, Panjehshahin MR | title = Partial least squares-based multivariate spectral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala seed extracts | journal = Analytica Chimica Acta | volume = 575 | issue = 2 | pages = 290–299 | date = August 2006 | pmid = 17723604 | doi = 10.1016/j.aca.2006.05.093 | bibcode = 2006AcAC..575..290H }}</ref> and 5.9%<ref>{{cite journal | vauthors = Herraiz T, González D, Ancín-Azpilicueta C, Arán VJ, Guillén H | title = beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO) | journal = Food and Chemical Toxicology | volume = 48 | issue = 3 | pages = 839–845 | date = March 2010 | pmid = 20036304 | doi = 10.1016/j.fct.2009.12.019 | hdl = 10261/77694 }}</ref> β-carboline alkaloids (by dry weight).

* A specific group of β-carboline derivatives, termed [[eudistomin]]s, were extracted from [[ascidian]]s (marine [[tunicates]] of the family ''[[Ascidiacea]]'') such as ''Ritterella sigillinoides'',<ref>{{cite journal |vauthors=Lake RJ, Blunt JW, Munro MH | title = Eudistomins from the New Zealand ascidian ''Ritterella sigillinoides'' | journal = Aust. J. Chem. | volume = 42 | issue = 7 | pages = 1201–1206 | year = 1989 | doi = 10.1071/CH9891201}}</ref> ''[[Lissoclinum fragile]]'' <ref>{{cite journal | vauthors = Badre A, Boulanger A, Abou-Mansour E, Banaigs B, Combaut G, Francisco C | title = Eudistomin U and isoeudistomin U, new alkaloids from the Caribbean ascidian Lissoclinum fragile | journal = Journal of Natural Products | volume = 57 | issue = 4 | pages = 528–533 | date = April 1994 | pmid = 8021654 | doi = 10.1021/np50106a016 }}</ref> or ''Pseudodistoma aureum''.<ref>{{cite journal | vauthors = Davis RA, Carroll AR, Quinn RJ | title = Eudistomin V, a new beta-carboline from the Australian ascidian Pseudodistoma aureum | journal = Journal of Natural Products | volume = 61 | issue = 7 | pages = 959–960 | date = July 1998 | pmid = 9677285 | doi = 10.1021/np9800452 }}</ref>

* [[Nostocarboline]] was isolated from freshwater [[cyanobacterium]].<ref>{{cite journal | vauthors = Becher PG, Beuchat J, Gademann K, Jüttner F | title = Nostocarboline: isolation and synthesis of a new cholinesterase inhibitor from Nostoc 78-12A | journal = Journal of Natural Products | volume = 68 | issue = 12 | pages = 1793–1795 | date = December 2005 | pmid = 16378379 | doi = 10.1021/np050312l }}</ref>

* The fully [[Aromaticity|aromatic]] β-carbolines also occur in many foodstuffs, however in lower concentrations. The highest amounts have been detected in brewed coffee, raisins, well done fish and meats.<ref>{{Citation|last=Herraiz|first=Tomás|title=β-Carbolines as Neurotoxins|date=2011-11-10|url=http://dx.doi.org/10.1007/978-1-4614-1542-8_5|work=Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants|pages=77–103|place=Boston, MA|publisher=Springer US|doi=10.1007/978-1-4614-1542-8_5 |isbn=978-1-4614-1541-1 |access-date=2021-11-16}}</ref> Smoking is another source of fully aromatic β-carbolines with levels up to thousands of µg per smoker each day.<ref>{{Cite journal|last1=Herraiz|first1=T.|last2=González|first2=D.|last3=Ancín-Azpilicueta|first3=C.|last4=Arán|first4=V.J.|last5=Guillén|first5=H.|date=March 2010|title=β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO)|url=http://dx.doi.org/10.1016/j.fct.2009.12.019|journal=Food and Chemical Toxicology|volume=48|issue=3|pages=839–845|doi=10.1016/j.fct.2009.12.019|pmid=20036304 |issn=0278-6915}}</ref>

* β-Carbolines have also been found in the [[cuticle]] of [[scorpion]]s, causing their skin to [[Fluorescence|fluoresce]] upon exposed to [[ultraviolet]] light at certain wavelengths (e.g. [[Black light|blacklight]]).<ref>{{cite journal | vauthors = Stachel SJ, Stockwell SA, Van Vranken DL | title = The fluorescence of scorpions and cataractogenesis | journal = Chemistry & Biology | volume = 6 | issue = 8 | pages = 531–539 | date = August 1999 | pmid = 10421760 | doi = 10.1016/S1074-5521(99)80085-4 | doi-access = free }}</ref>

== See also ==

* [[Gamma-carboline]]

* [[Oxopropaline]]<ref>{{cite journal|vauthors=Abe N, Nakakita Y, Nakamura T, Enoki N, Uchida H, Takeo S, Munekata M |year=1993|title=Novel cytocidal compounds, oxopropalines from Streptomyces sp. G324 producing lavendamycin. I. Taxonomy of the producing organism, fermentation, isolation and biological activities|volume=46|issue=11|pages=1672–1677|pmid=8270488|journal=J. Antibiot.|doi=10.7164/antibiotics.46.1672|doi-access=free}}</ref>

== References ==

== External links ==

* {{MeshName|Beta-Carbolines}}

* [http://www.biopsychiatry.com/coffee-maoi.htm Beta-carbolines in coffee]

* {{cite journal | vauthors = Farzin D, Mansouri N | title = Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test | journal = European Neuropsychopharmacology | volume = 16 | issue = 5 | pages = 324–328 | date = July 2006 | pmid = 16183262 | doi = 10.1016/j.euroneuro.2005.08.005 | s2cid = 54410407 }}

{{GABAergics}}

[[Category:Anxiolytics]]

[[Category:Convulsants]]

[[Category:GABAA receptor negative allosteric modulators]]

[[Category:Indole alkaloids]]