Harmaline

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Harmaline
Harmalin.svg
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Clinical data
Dependence
liability
N/A
Routes of
administration
Ingestion
Legal status
Legal status
Identifiers
  • 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
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Chemical and physical data
Formula C13H14N2O
Molar mass 214.268 g·mol−1
3D model (JSmol)
Melting point 232–234 °C (450–453 °F)
  • COc3ccc2c1CCN=C(C)c1[nH]c2c3
  • InChI=1S/C13H14N2O/c1-8-13-11(5-6-14-8)10-4-3-9(16-2)7-12(10)15-13/h3-4,7,15H,5-6H2,1-2H3 Yes check.svgY
  • Key:RERZNCLIYCABFS-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine.

Contents

Occurrence in nature

Various plants contain harmaline including Peganum harmala (Syrian rue) as well as the hallucinogenic beverage ayahuasca, which is traditionally brewed using Banisteriopsis caapi . Present at 3% by dry weight, the harmala alkaloids may be extracted from the Syrian rue seeds. [1]

Effects

Harmaline is a central nervous system stimulant and a "reversible inhibitor of MAO-A (RIMA)". [2] This means that the risk of a hypertensive crisis, a dangerous high blood pressure crisis from eating tyramine-rich foods such as cheese, is likely lower with harmaline than with irreversible MAOIs such as phenelzine.

Harmaline and harmine fluoresce under ultraviolet light. These three extractions indicate that the middle one has a higher concentration of the two compounds. Harmaline Harmine.jpg
Harmaline and harmine fluoresce under ultraviolet light. These three extractions indicate that the middle one has a higher concentration of the two compounds.

The harmala alkaloids are psychoactive in humans. [1] Harmaline is shown to act as an acetylcholinesterase inhibitor. [3] Harmaline also stimulates striatal dopamine release in rats at very high dose levels. [4] Since harmaline is a reversible inhibitor of monoamine oxidase A, it could, in theory, induce both serotonin syndrome and hypertensive crises in combination with tyramine, serotonergics, catecholaminergics drugs or prodrugs. Harmaline-containing plants and tryptamine-containing plants are used in ayahuasca brews. The inhibitory effects on monoamine oxidase allows dimethyltryptamine (DMT), the psychoactively prominent chemical in the mixture, to bypass the extensive first-pass metabolism it undergoes upon ingestion, allowing a psychologically active quantity of the chemical to exist in the brain for a perceivable period of time. [5] Harmaline forces the anabolic metabolism of serotonin into N-acetylserotonin (normelatonin), and then to melatonin, the body's principal sleep-regulating hormone and a powerful antioxidant.

United States Patent Number 5591738 describes a method for treating various chemical dependencies via the administration of harmaline and or other beta-carbolines. [6]

A study has reported the antiviral activity of Harmaline against Herpes Simplex Virus 1 and 2 (HSV-1 and HSV-2) by inhibiting immediate early transcription of the virus at noncytotoxic concentration. [7]

Harmaline is known to act as a histamine N-methyltransferase inhibitor. [8] This explains how harmaline elicits its wakefulness-promoting effects.

Australia

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015). [9] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities. [9]

Canada

Harmaline and Harmalol are considered Schedule III controlled substances by the Controlled Drugs and Substances Act. Every person found to be in possession of a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding three years; or for a first offence, guilty on summary conviction, to a fine not exceeding one thousand dollars or to imprisonment for a term not exceeding six months, or to both. Every person found to be trafficking a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding ten years, or is guilty on summary conviction (first-time offenders) and liable to imprisonment for a term not exceeding eighteen months. [10]

See also

Related Research Articles

<span class="mw-page-title-main">Ayahuasca</span> South American psychoactive brew

Ayahuasca is a South American psychoactive brew, traditionally used by Indigenous cultures and folk healers in Amazon and Orinoco basins for spiritual ceremonies, divination, and healing a variety of psychosomatic complaints. Originally restricted to areas of Peru, Brazil, Colombia and Ecuador, in the middle of 20th century it became widespread in Brazil in context of appearance of syncretic religions that uses ayahuasca as a sacrament, like Santo Daime, União do Vegetal and Barquinha, which blend elements of Amazonian Shamanism, Christianity, Kardecist Spiritism, and African-Brazilian religions such as Umbanda, Candomblé and Tambor de Mina, later expanding to several countries across all continents, notably the United States and Western Europe, and, more incipiently, in Eastern Europe, South Africa, Australia, and Japan.

<i>N</i>,<i>N</i>-Dimethyltryptamine Chemical compound

N,N-Dimethyltryptamine is a substituted tryptamine that occurs in many plants and animals, including humans, and which is both a derivative and a structural analog of tryptamine. DMT is used as a psychedelic drug and prepared by various cultures for ritual purposes as an entheogen.

α-Methyltryptamine Chemical compound

α-Methyltryptamine is a psychedelic, stimulant, and entactogen drug of the tryptamine class. It was originally developed as an antidepressant by chemists at Upjohn in the 1960s, and was used briefly as an antidepressant in Russia under the trade name Indopan before being discontinued.

<i>Banisteriopsis caapi</i> Species of plant

Banisteriopsis caapi, also known as, caapi, soul vine, or yagé (yage), is a South American liana of the family Malpighiaceae. It is commonly used as an ingredient of ayahuasca, a decoction with a long history of its entheogenic use and its status as a "plant teacher" among the Indigenous peoples of the Amazon rainforest.

β-Carboline Chemical compound also known as norharmane

β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids 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 effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties.

<span class="mw-page-title-main">Harmala alkaloid</span> Group of chemical compounds

Harmala alkaloids are several alkaloids that increase effects of reward system neurotransmitter dopamine by acting as monoamine oxidase inhibitors (MAOIs). These alkaloids are found in the seeds of Peganum harmala, as well as leaves of tobacco and coffee beans. The alkaloids include harmine, harmaline, harmalol, and their derivatives, which have similar chemical structures, hence the name "harmala alkaloids". These alkaloids are of interest for their use in Amazonian shamanism, where they are derived from other plants. Harmine, once known as telepathine and banisterine, is a naturally occurring beta-carboline alkaloid that is structurally related to harmaline, and also found in the vine Banisteriopsis caapi. Tetrahydroharmine is also found in B. caapi and P. harmala. Dr. Alexander Shulgin has suggested that harmine may be a breakdown product of harmaline. Harmine and harmaline are reversible inhibitors of monoamine oxidase A (RIMAs). They can stimulate the central nervous system by inhibiting the metabolism of monoamine compounds such as serotonin and norepinephrine.

<i>Peganum harmala</i> Species of plant

Peganum harmala, commonly called wild rue, Syrian rue, African rue, esfand or espand, or harmel, is a perennial, herbaceous plant, with a woody underground rootstock, of the family Nitrariaceae, usually growing in saline soils in temperate desert and Mediterranean regions. Its common English-language name came about because of a resemblance to rue. Because eating it would sicken or kill livestock, it is considered a noxious weed in a number of countries. It has become an invasive species in some regions of the western United States. The plant is popular in Middle Eastern and north African folk medicine. The alkaloids contained in the plant, including the seeds, are monoamine oxidase inhibitors.

<span class="mw-page-title-main">Diethyltryptamine</span> Chemical compound

DET, also known under its chemical name N,N-diethyltryptamine and as T-9, is a psychedelic drug closely related to DMT and 4-HO-DET. However, despite its structural similarity to DMT, its activity is induced by an oral dose of around 50–100 mg, without the aid of MAO inhibitors, and the effects last for about 2–4 hours.

<i>Psychotria viridis</i> Perennial flowering plant in the coffee family Rubiaceae

Psychotria viridis, also known as chacruna, chacrona, or chaqruy in the Quechua languages, is a perennial, shrubby flowering plant in the coffee family Rubiaceae. It is a close relative of Psychotria carthagenensis of Ecuador. It is commonly used as an ingredient of ayahuasca, a decoction with a long history of its entheogenic use and its status as a "plant teacher" among the Indigenous peoples of the Amazon rainforest.

Harmine is a beta-carboline and a harmala alkaloid. It occurs in a number of different plants, most notably the Syrian rue and Banisteriopsis caapi. Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamines, making it a Reversible inhibitor of monoamine oxidase A (RIMA). Harmine does not inhibit MAO-B. Harmine is also known as banisterin, banisterine, telopathin, telepathine, leucoharmine and yagin, yageine.

<span class="mw-page-title-main">Tetrahydroharmine</span> Chemical compound

Tetrahydroharmine (THH) is a fluorescent indole alkaloid that occurs in the tropical liana species Banisteriopsis caapi.

Pharmahuasca is a pharmaceutical version of the entheogenic brew ayahuasca. Traditional ayahuasca is made by brewing the MAOI-containing Banisteriopsis caapi vine with a DMT-containing plant, such as Psychotria viridis. Pharmahuasca refers to a similar combination that uses a pharmaceutical MAOI instead of a plant.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.

<span class="mw-page-title-main">Harmalol</span> Chemical compound

Harmalol is a bioactive beta-carboline and a member of the harmala alkaloids.

<span class="mw-page-title-main">Tetrahydroharmol</span> Chemical compound

Tetrahydroharmol is a bioactive beta-carboline harmala alkaloid. It acts as a reversible inhibitor of monoamine oxidase A.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

<span class="mw-page-title-main">Harmane</span> Chemical compound

Harmane (harman) is a heterocyclic amine found in a variety of foods including coffee, sauces, and cooked meat. It is also present in tobacco smoke.

<span class="mw-page-title-main">Harmol</span> Chemical compound

Harmol is a chemical compound classified as a β-carboline. It is readily formed in vivo in humans by O-demethylation of harmine.

<span class="mw-page-title-main">Changa (drug)</span> DMT-infused smoking blend

Changa is a blend of N,N-Dimethyltryptamine (DMT) mixed with a monoamine oxidase inhibitor (MAOI). The addition of MAOIs extends the DMT experience in duration and intensity when compared with smoking DMT freebase alone. Typically, extracts from DMT-containing plants are combined with a blend of different MAOI-containing herbs, such as the ayahuasca vine, and/or leaf or harmala alkaloids from Peganum harmala to create a mix that is 25 to 50% DMT.

References

  1. 1 2 "Peganum Harmala pamphlet: Syrian Rue". Erowid.
  2. Massaro EJ (2002). Handbook of Neurotoxicology. Totowa, NJ: Humana Press. p. 237. ISBN   978-0-89603-796-0.
  3. Zheng XY, Zhang ZJ, Chou GX, Wu T, Cheng XM, Wang CH, Wang ZT (September 2009). "Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of Peganum nigellastrum Bunge by an in vitro TLC- bioautographic assay". Archives of Pharmacal Research. 32 (9): 1245–51. doi:10.1007/s12272-009-1910-x. PMID   19784581. S2CID   1218229.
  4. Schwarz MJ, Houghton PJ, Rose S, Jenner P, Lees AD (June 2003). "Activities of extract and constituents of Banisteriopsis caapi relevant to parkinsonism". Pharmacology, Biochemistry, and Behavior. 75 (3): 627–33. doi:10.1016/S0091-3057(03)00129-1. PMID   12895680. S2CID   28243440.
  5. Shen HW, Jiang XL, Winter JC, Yu AM (October 2010). "Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions". Current Drug Metabolism. 11 (8): 659–66. doi:10.2174/138920010794233495. PMC   3028383 . PMID   20942780.
  6. USpatent 5591738,Lotsof H,"Method of Treating Chemical Dependency Using β-Carboline Alkaloids, Derivatives and Salts thereof",issued 1997-01-07, assigned to NDA Int Inc
  7. Bag P, Ojha D, Mukherjee H, Halder UC, Mondal S, Biswas A, Sharon A, Van Kaer L, Chakrabarty S, Das G, Mitra D, Chattopadhyay D (May 2014). "A dihydro-pyrido-indole potently inhibits HSV-1 infection by interfering the viral immediate early transcriptional events". Antiviral Research. 105: 126–134. doi:10.1016/j.antiviral.2014.02.007. PMID   24576908.
  8. Cumming P, Vincent SR (September 1992). "Inhibition of histamine-N-methyltransferase (HNMT) by fragments of 9-amino-1,2,3,4-tetrahydroacridine (tacrine) and by beta-carbolines". Biochemical Pharmacology. 44 (5): 989–92. doi:10.1016/0006-2952(92)90133-4. PMID   1530666.
  9. 1 2 "Poisons Standard October 2015". Australian Government. 30 September 2015.
  10. "Controlled Drugs and Substances Act (S.C 1996, c.19)". Justice Laws Website. 19 September 2019. Retrieved 25 September 2019.

Further reading