Harmine

Harmine
IUPAC name 7-MeO-1-Me-9H -pyrido[3,4-b]-indole
Identifiers
CAS number	442-51-3 Y
PubChem	5280953
ChemSpider	4444445 Y
UNII	4FHH5G48T7 Y
DrugBank	DB07919
KEGG	C06538 Y
ChEBI	CHEBI:28121 Y
ChEMBL	CHEMBL269538 Y
Jmol-3D images	Image 1
SMILES n3ccc2c1c(cc(OC)cc1)nc2c3C
InChI InChI=1S/C13H12N2O/c1-8-13-11(5-6-14-8)10-4-3-9(16-2)7-12(10)15-13/h3-7,15H,1-2H3 Y Key: BXNJHAXVSOCGBA-UHFFFAOYSA-N Y InChI=1/C13H12N2O/c1-8-13-11(5-6-14-8)10-4-3-9(16-2)7-12(10)15-13/h3-7,15H,1-2H3 Key: BXNJHAXVSOCGBA-UHFFFAOYAR
Properties
Molecular formula	C13H12N2O
Molar mass	212.25 g/mol
Melting point	321 °C (·HCl); 262 °C (·HCl·2H2O)[1]
Solubility in water	insoluble[2]
Solubility in DMSO	100mM[3]
Solubility in Ethanol	1 mg/mL[4]
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Harmine is a fluorescent harmala alkaloid belonging to the beta-carboline family of compounds. It occurs in a number of different plants, most notably the Middle Eastern plant harmal or Syrian rue (Peganum harmala) and the South American vine Banisteriopsis caapi (also known as "yage" or "ayahuasca"). Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamines, making it a RIMA. Harmine selectively binds to MAO-A but does not inhibit the variant MAO-B.^[5]

Uses

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

Monoamines include neurotransmitters (serotonin, dopamine), hormones (melatonin, epinephrine, norepinephrine) and psychedelic drugs (psilocybin, DMT and mescaline). By slowing the breakdown of neurotransmitters, monoamine oxidase inhibitors (MAOIs) can help to replenish the body's supply of these chemicals, and many MAOIs are used as antidepressants. Harmine has not been the subject of much clinical research in the treatment of depression, which could be due in part to its restricted legal status in many countries, as well as the existence of synthetic MAOIs with fewer side effects.

P. harmala and B. caapi are both traditionally used for their psychoactive effects. B. caapi has a tradition of use in conjunction with plants containing the drug DMT. Traditionally, B. caapi is consumed as a drink, with or without the DMT-bearing plants (see Ayahuasca). Ordinarily, DMT is not active when taken orally, but users report very different effects when DMT is present in such beverages. Harmine and substances containing it have been used in conjunction with many other drugs by modern experimenters. Many hallucinogens appear to exhibit increased potency when used in this way.

Harmine is also a useful fluorescent pH indicator. As the pH of its local environment increases, the fluorescence emission of harmine decreases.

With the radioisotope carbon-11 harmine is used in positron emission tomography neuroimaging to examine its binding to MAO-A.^[6]

Harmine found in root secretions of Oxalis tuberosa has been found to have insecticidal properties.^[7]

Harmine has been found to increase EAAT2 glutamate pump expression in central nervous system, therefore reducing glutamate toxicity.^[8]

Anticancer

"Harmine showed cytotoxicity against HL60 and K562 cell lines. This could explain the cytotoxic effect of P. harmala on these cells."^[9]

Adverse effects

Harmine, and plants containing significant amounts of harmine and other harmala alkaloids are generally not considered safe treatments for depression within the medical community. This bias however is primarily built on previous decades of experience with pharmaceutical non-specific MAOIs that block both MAO-A and MAO-B.^[10] Inhibiting MAO-A or MAO-B (in high enough doses) while consuming foods rich in tyramine, e.g. cheese, can cause tyramine, ordinarily metabolized by these enzymes, to accumulate to dangerous levels. This can cause a potentially fatal hypertensive crisis. Because harmine reversibly and selectively inhibits MAO-A and does not degrade MAO-B, MAO-B remains free to metabolize tyramine in the digestive tract. Consequently, the harmala alkaloids (including harmine) are unlikely to elicit tyramine-mediated hypertensive crisis, and a special diet does not need to be so strictly adhered to. Nonetheless, due to the reduction of the levels of tyramine degrading compounds in the gut, it is still not advisable to eat excessively large amounts of tyramine-rich food products.^[11] The reversibility and MAO-A selectivity of harmala alkaloids do not, however, prevent potentially fatal interactions with common medications such as antihistamines, most antidepressants, many stimulants, common migraine medications, some herbs, decongestants, expectorants, and common cough and cold medications.

It has recently been shown in the Journal of Photochemistry and Photobiology B: Biology that beta-carboline MAO inhibitors, such as harmine, bind with DNA and also exhibit anti-tumor properties. Harmine has been shown to bind one hundred times more effectively than its close analogue harmaline. The consequences of this are currently not well understood.^[12]

Rapid discontinuation of MAO inhibitors can cause serious withdrawal syndrome .

Overdosage

Oral or intravenous harmine doses ranging from 30–300 mg have caused agitation, bradycardia or tachycardia, blurred vision, hypotension, paresthesias and hallucinations. Serum or plasma harmine concentrations may be measured as a confirmation of diagnosis. The plasma elimination half-life is on the order of 1–3 hours.^[13]

Natural sources

Harmine is found in a wide variety of different organisms, most of which are plants. Shulgin^[14] lists about thirty different species known to contain harmine, including seven species of butterfly in the Nymphalidae family. The harmine-containing plants listed include tobacco, two species of passion flower/passion fruit, and numerous others. Lemon Balm contains Harmine.^[15]

In addition to B. caapi, at least three members of the Malpighiaceae contain harmine, including two more Banisteriopsis species and the plant Callaeum antifebrile. Callaway, Brito and Neves (2005)^[16] found harmine levels of 0.31-8.43% in B. caapi samples.

The Zygophyllaceae family, which harmal belongs to, contains at least two other harmine-bearing plants: Peganum nigellastrum and Zygophyllum fabago.

See also

• Monoamine oxidase inhibitor

References

External links

• Harmine found in Oxalis tuberosa
• Harmine entry in TiHKAL • info