Гармин: Химические свойства и биологическая активность

chembox
| Watchedfields = changed
| verifiedrevid = 443852670
| Name = Harmine
| ImageFileL1 = Harmine structure. svg
| ImageFileR1 = Harmine 3d structure. png
| ImageName = Harmine
| PIN = 7 Methoxy 1 methyl 9H pyrido[3,4 b]indole
| Section1 =
| Section2 = Chembox Properties
| Formula = C13H12N2O
| MolarMass = 212.25 g/mol
| MeltingPtC = 321
| MeltingPt notes = (·HCl); 262 °C (·HCl·2H2O)
| Density = 1.326 g/cm3
| Solubility = insoluble
| Solvent1 = Dimethyl sulfoxide
| Solubility1 = 100mM 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.

The coincident occurrence of β carboline alkaloids and serotonin in Peganum harmala indicates the presence of two very similar, interrelated biosynthetic pathways, which makes it difficult to definitively identify whether free tryptamine or L tryptophan is the precursor in the biosynthesis of harmine. However, it is postulated that L tryptophan is the most likely precursor, with tryptamine existing as an intermediate in the pathway. The following figure shows the proposed biosynthetic scheme for harmine. The Shikimate acid pathway yields the aromatic amino acid, L tryptophan. Decarboxylation of L tryptophan by aromatic L amino acid decarboxylase (AADC) produces tryptamine (I), which contains a nucleophilic center at the C 2 carbon of the indole ring due to the adjacent nitrogen atom that enables the participation in a Mannich type reaction. Rearrangements enable the formation of a Schiff base from tryptamine, which then reacts with pyruvate in II to form a β carboline carboxylic acid. The β carboline carboxylic acid subsequently undergoes decarboxylation to produce 1 methyl β carboline III. Hydroxylation followed by methylation in IV yields harmaline. The order of O methylation and hydroxylation have been shown to be inconsequential to the formation of the harmaline intermediate. Medically significant amounts of harmine occur in the plants Syrian rue and Banisteriopsis caapi. These plants also contain notable amounts of harmaline, Syrian rue or synthetic harmine is sometimes used to substitute B. caapi in the oral use of DMT.

Harmine is a useful fluorescent pH indicator. As the pH of its local environment increases, the fluorescence emission of harmine decreases. Due to its MAO A specific binding, carbon 11 labeled harmine can be used in positron emission tomography to study MAO A dysregulation in several psychiatric and neurologic illnesses. Harmine was used as an antiparkinsonian medication since the late 1920s until the early 1950s. It was replaced by other medications. These islet sub cells are normally resistant to growth stimulation in the adult stage of a human's life, as the cell mass plateaus at around age 10 and remains virtually unchanged.

Harmine has been found to be relatively toxic to humans where symptoms arise at 3mg/kg. These symptoms include behavioral changes such as sleep, tremors, gastrointestinal issues, nausea and vomiting.

Harmine is found in a wide variety of different organisms, most of which are plants. Alexander Shulgin lists about thirty different species known to contain harmine, including seven species of butterfly in the family Nymphalidae. The harmine containing plants include tobacco, Peganum harmala, two species of passiflora, and numerous others. Lemon balm (Melissa officinalis) contains harmine. 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) found harmine levels of 0.31 8.43% in B. caapi samples. The family Zygophyllaceae, which P. harmala belongs to, contains at least two other harmine bearing plants: Peganum nigellastrum and Zygophyllum fabago.

J. Fritzsche was the first to isolate and name harmine. He isolated it from the husks of Peganum harmala seeds in 1848. The related harmaline was already isolated and named by Fr. Göbel in 1837 from the same plant. In 1905, the Colombian naturalist and chemist, Rafael Zerda Bayón suggested the name telepathine to the then unknown hallucinogenic ingredient in ayahuasca brew. In 1923, the Colombian chemist, Guillermo Fischer Cárdenas was the first to isolate harmine from Banisteriopsis caapi, which is an important herbal component of ayahuasca brew. He called the isolated harmine "telepathine". In 1925, Barriga Villalba, professor of chemistry at the University of Bogotá, isolated harmine from B. caapi, but named it "yajéine", which in some texts is written as "yageine". but this supposedly novel compound was soon also shown to be harmine.

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015). 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. Exceptions are made when in herbs, or preparations, for therapeutic use such as: (a) containing 0.1 per cent or less of harmala alkaloids; or (b) in divided preparations containing 2 mg or less of harmala alkaloids per recommended daily dose.