A substituted β-carboline is a

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

featuring a β-carboline moiety with one or more substitutions. β-Carbolines include more than one hundred

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

s and synthetic compounds. The effects of these substances depend on their respective

substituent In organic chemistry, a substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. The suffix ''-yl'' is used when naming organic compounds that contain a single bond r ...

. Natural β-carbolines primarily influence

brain functions The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for special senses s ...

but can also exhibit

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

properties. β-Carbolines are

indole alkaloids Indole alkaloids are a class of alkaloids containing a Moiety (chemistry), structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than ...

featuring a fused

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

and

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

ring structure similar to

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the firs ...

, forming a three-ringed system with variable saturation in the third ring. β-Carboline

s naturally occur widely in

prokaryote A prokaryote (; less commonly spelled procaryote) is a unicellular organism, single-celled organism whose cell (biology), cell lacks a cell nucleus, nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Gree ...

plant Plants are the eukaryotes that form the Kingdom (biology), kingdom Plantae; they are predominantly Photosynthesis, photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with c ...

animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

s, certain marine

tunicate Tunicates are marine invertebrates belonging to the subphylum Tunicata ( ). This grouping is part of the Chordata, a phylum which includes all animals with dorsal nerve cords and notochords (including vertebrates). The subphylum was at one time ...

s, and foods like

coffee Coffee is a beverage brewed from roasted, ground coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulating effect on humans, primarily due to its caffeine content, but decaffeinated coffee is also commercially a ...

and smoked

meat Meat is animal Tissue (biology), tissue, often muscle, that is eaten as food. Humans have hunted and farmed other animals for meat since prehistory. The Neolithic Revolution allowed the domestication of vertebrates, including chickens, sheep, ...

s, and are also responsible for the fluorescence of

scorpion Scorpions are predatory arachnids of the Order (biology), order Scorpiones. They have eight legs and are easily recognized by a pair of Chela (organ), grasping pincers and a narrow, segmented tail, often carried in a characteristic forward cur ...

cuticles under

ultraviolet Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of ...

light. β-Carbolines occurring naturally in ''

Peganum harmala ''Peganum harmala'', commonly called wild rue, Syrian rue, African rue, esfand or espand,Mahmoud OmidsalaEsfand: a common weed found in Persia, Central Asia, and the adjacent areasEncyclopædia Iranica Vol. VIII, Fasc. 6, pp. 583–584. Origina ...

'' (Syrian rue) are known as

harmala alkaloid Harmala alkaloids are several alkaloids that act as monoamine oxidase inhibitors (MAOIs). These alkaloids are found in the seeds of ''Peganum harmala'' (also known as harmal or Syrian rue), as well as ''Banisteriopsis caapi'' (ayahuasca), leave ...

s. Some β-carbolines, like

harmaline Harmaline, also known as 7-methoxyharmalan or as 3,4-dihydro-7-methoxy-1-methyl-β-carboline, is a fluorescent indole alkaloid from the group of harmala alkaloids and β-carbolines. It is the partly hydrogenated form of harmine. It is a rever ...

, are

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic. According to

Alexander Shulgin Alexander Theodore "Sasha" Shulgin (June 17, 1925 – June 2, 2014) was an American biochemist, broad researcher of synthetic psychoactive compounds, and author of works regarding these, who independently explored the organic chemistry and ph ...

, harmaline is the only β-carboline that has been extensively studied and well-established as a hallucinogen. β-Carbolines are known to act as

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

s (MAOIs), among possessing other activities. They are an essential component of

ayahuasca AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' (Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' descen ...

, by inhibiting the

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

of the

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

(DMT).

Use and effects

As hallucinogens

β-Carbolines are cyclized tryptamines related to

serotonergic psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluci ...

s like

(DMT) and

5-MeO-DMT 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine), also known as ''O''-methylbufotenin or mebufotenin (), is a naturally occurring psychedelic of the tryptamine family. It is found in a wide variety of plant species, and is also secreted by ...

. Some simple β-carbolines have been reported to be

ic. These include harmine,

, tetrahydroharmine,

6-methoxyharmalan 6-Methoxyharmalan, or 6-methoxyharmalane, also known as 6-methoxy-1-methyl-3,4-dihydro-β-carboline, is a naturally occurring serotonin receptor modulator, monoamine oxidase inhibitor, and hallucinogen of the β-carboline family related to harm ...

, and 6-methoxytetrahydroharman (6-MeO-THH). According to

however, harmaline is the only β-carboline that has been extensively studied and well-established as a hallucinogen. β-Carbolines are active both orally and parenterally, with doses, depending on the compound, in the area of 100 to 300mg or more orally and 1 to 1.5mg/kg (~70–100mg for a 70-kg person)

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. Although structurally related to psychedelic tryptamines, the hallucinogenic effects of β-carbolines are said to be qualitatively distinct from those of serotonergic psychedelics. Instead, they are described as being similar to those of

ibogaine Ibogaine is a psychoactive indole alkaloid derived from plants such as '' Tabernanthe iboga'', characterized by hallucinogenic and oneirogenic effects. Traditionally used by Central African foragers, it has undergone controversial research ...

, which is also a cyclized tryptamine and structurally related atypical hallucinogen.

Pharmacology

The pharmacological effects of specific β-carbolines are dependent on their

s. For example, the natural β-carboline harmine has substituents on position 7 and 1. Thereby, it acts as a selective

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

of the

DYRK1A Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the ''DYRK1A'' gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or ...

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...

, a protein necessary for

neurodevelopment The development of the nervous system in humans, or neural development, or neurodevelopment involves the studies of embryology, developmental biology, and neuroscience. These describe the cellular and molecular mechanisms by which the complex ...

. It also exhibits various

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

-like effects in rats by interacting with serotonin receptor 2A. Furthermore, it increases levels of the

brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the can ...

(

BDNF Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the cano ...

) in rat

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

. A decreased BDNF level has been associated with major depression in humans. The antidepressant effect of harmine might also be due to its function as a MAO-A inhibitor by reducing the breakdown of

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

and

noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as a hormone, neurotransmitter and neuromodulator. The name "noradrenaline" (from ...

. A synthetic

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

9-methyl-β-carboline 9-Methyl-β-carboline (9-Me-BC) is a heterocyclic amine of the β-carboline family, and a research chemical sometimes used as a nootropic. It is a monoamine oxidase inhibitor, primarily of MAO-A. In mice studies, it has been found to stimulate ...

, has shown neuroprotective effects including increased expression of

neurotrophic factors Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and cell differentiation, differentiation of both developing and mature neurons. Most ...

and enhanced

respiratory chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this ...

activity. This derivative has also been shown to enhance

cognitive function Cognitive skills are skills of the mind, as opposed to other types of skills such as motor skills, social skills or life skills. Some examples of cognitive skills are literacy, self-reflection, logical reasoning, abstract thinking, critical th ...

, increase

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neuron count and facilitate synaptic and

dendritic Dendrite derives from the Greek word "dendron" meaning ( "tree-like"), and may refer to: Biology *Dendrite, a branched projection of a neuron *Dendrite (non-neuronal), branching projections of certain skin cells and immune cells Physical *Dendri ...

proliferation. It also exhibited therapeutic effects in animal models for

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

and other

neurodegenerative A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

processes. However, β-carbolines with substituents in position 3 reduce the effect of

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

on GABA-A receptors and can therefore have

convulsive A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synonym ...

anxiogenic An anxiogenic or panicogenic substance is one that causes anxiety. This effect is in contrast to anxiolytic agents, which inhibits anxiety. Together these categories of psychoactive compounds may be referred to as anxiotropic compounds. Experime ...

and memory enhancing effects. 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. Another derivative, methyl-β-carboline-3-carboxylate, stimulates learning and memory at low doses but can promote anxiety and convulsions at high doses. With modification in position 9 similar positive effects have been observed for learning and memory without promotion of anxiety or convulsion. β-carboline derivatives also enhance the production of the

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

reveromycin A in soil-dwelling ''

Streptomyces ''Streptomyces'', from στρεπτός (''streptós''), meaning "twisted", and μύκης (''múkés''), meaning "fungus", is the largest genus of Actinomycetota, and the type genus of the family Streptomycetaceae. Over 700 species of ''St ...

'' species. Specifically, expression of

biosynthetic Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme- catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s is facilitated by binding of the β-carboline to a large ATP-binding regulator of the LuxR family. Also Lactobacillus spp. secretes a β-carboline (1-acetyl-β-carboline) preventing the pathogenic fungus

Candida albicans ''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is usu ...

to change to a more

virulent Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most cases, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its abilit ...

growth form (yeast-to-filament transition). Thereby, β-carboline reverses imbalances in the

microbiome A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably wel ...

composition causing pathologies ranging from vaginal candidiasis to fungal sepsis. Since β-carbolines also interact with various

-related molecules such as

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s ( GPX4,

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

s, etc.) and

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s (

ABCG2 ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ''ABCG2'' gene. ABCG2 has also been designated as CDw338 (cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs ...

/BRCP1, etc.), they are also discussed as potential anticancer agents.

Hallucinogenic activity

The hallucinogenic effects of β-carbolines are said to be qualitatively distinct from those of

s like

mescaline Mescaline, also known as mescalin or mezcalin, and in chemical terms 3,4,5-trimethoxyphenethylamine, is a natural product, naturally occurring psychedelic drug, psychedelic alkaloid, protoalkaloid of the substituted phenethylamine class, found ...

but similar to those of

. Along these lines, β-carbolines and ibogaine fully substitute for each other in rodent

drug discrimination Drug discrimination (DD) is a technique in behavioral neuroscience used to evaluate the discriminative stimulus properties or interoceptive cues of psychoactive drugs. In drug discrimination, a subject is trained on a training drug, and then i ...

tests. The

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

of hallucinogens of the β-carboline and ibogaine type is unclear. Findings are conflicting on whether

5-HT_2A receptor

activation In chemistry and biology, activation is the process whereby something is prepared or excited for a subsequent reaction. Chemistry In chemistry, "activation" refers to the reversible transition of a molecule into a nearly identical chemical or ...

may be involved or not. β-Carbolines and ibogaine do have low

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the serotonin 5-HT_2A receptor, but β-carbolines failed to activate the receptor even at high concentrations. β-Carbolines and ibogaine show stimulus generalization with serotonergic psychedelics like DOM and

LSD Lysergic acid diethylamide, commonly known as LSD (from German ; often referred to as acid or lucy), is a semisynthetic, hallucinogenic compound derived from ergot, known for its powerful psychological effects and serotonergic activity. I ...

in rodent

tests and this generalization can be blocked by serotonin 5-HT₂ receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. On the other hand, a fairly selective serotonin 5-HT_2A receptor antagonist did not affect harmaline's substitution of ibogaine in rodent drug discrimination tests. Moreover, unlike psychedelics, ibogaine does not produce the

head-twitch response The head-twitch response (HTR), also sometimes known as wet dog shakes (WDS) in rats, is a rapid side-to-side head movement that occurs in mice and rats in association with serotonin 5-HT2A receptor activation. Serotonergic psychedelics like lys ...

in rodents.

Monoamine oxidase inhibition and Parkinson's disease

The extract of the

liana A liana is a long-Plant stem, stemmed Woody plant, woody vine that is rooted in the soil at ground level and uses trees, as well as other means of vertical support, to climb up to the Canopy (biology), canopy in search of direct sunlight. T ...

Banisteriopsis caapi ''Banisteriopsis caapi'', also known as, caapi, soul vine, yagé (yage), or ayahuasca (the latter of which also refers to the psychedelic decoction made with the vine and a plant source of dimethyltryptamine) is a South American liana of the fam ...

'' has been used by the tribes of the

Amazon Amazon most often refers to: * Amazon River, in South America * Amazon rainforest, a rainforest covering most of the Amazon basin * Amazon (company), an American multinational technology company * Amazons, a tribe of female warriors in Greek myth ...

as an

entheogen Entheogens are psychoactive substances used in spiritual and religious contexts to induce altered states of consciousness. Hallucinogens such as the psilocybin found in so-called "magic" mushrooms have been used in sacred contexts since ancie ...

and was described as a

in the middle of the 19th century. In early 20th century, European pharmacists identified harmine as the active substance. This discovery stimulated the interest to further investigate its potential as a medicine. For example,

Louis Lewin Louis Lewin (9 November 1850 - 1 December 1929) was a German pharmacologist. In 1887 he received his first sample of the Peyote, Peyote cactus from Dallas, Texas-based physician John Raleigh Briggs (1851-1907), and later published the first metho ...

, a prominent pharmacologist, demonstrated a dramatic benefit in neurological impairments after injections of ''B. caapi'' in patients with

postencephalitic Parkinsonism Post-encephalitic parkinsonism is a disease believed to be caused by a viral illness that triggers degeneration of the nerve cells in the substantia nigra. Overall, this degeneration leads to clinical parkinsonism. Historically, starting in 1917 a ...

. By 1930, it was generally agreed that

hypokinesia Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a sy ...

drooling Drooling, or slobbering, is the flow of saliva outside the mouth. Drooling can be caused by excess production of saliva, inability to retain saliva within the mouth (incontinence of saliva), or problems with swallowing (dysphagia or odynophagia) ...

, mood, and sometimes rigidity improved by treatment with harmine. Altogether, 25 studies had been published in the 1920s and 1930s about patients with

and postencephalitic Parkinsonism. The pharmacological effects of harmine have been attributed mainly to its central

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The fi ...

(MAO) inhibitory properties.

In-vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

and rodent studies have shown that extracts of ''Banisteriopsis caapi'' and also ''

'' lead to striatal

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

release. Furthermore, harmine supports the survival of dopaminergic neurons in

MPTP MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine. It is of interest as a precursor to the monoaminergic neurotoxin MPP+, which causes permanent symptoms of Parkinson's dise ...

-treated mice. Since harmine also antagonizes ''N''-methyl-d-aspartate (NMDA) receptors, some researchers speculatively attributed the rapid improvement in patients with Parkinson's disease to these antiglutamatergic effects. However, the advent of synthetic

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

drugs at that time led to the total abandonment of harmine.

Chemical structure

β-Carbolines belong to the group of

and consist of a pyridine ring that is fused to an

skeleton. The structure of β-carboline is similar to that of

, with the

ethylamine Ethylamine, also known as ethanamine, is an organic compound with the chemical formula, formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscibility, miscible with virtual ...

chain re-connected to the

ring via an extra

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

atom, to produce a three-ringed structure. The biosynthesis of β-carbolines is believed to follow this route from analogous tryptamines. Different levels of

saturation Saturation, saturated, unsaturation or unsaturated may refer to: Chemistry *Saturated and unsaturated compounds, a classification of compounds related to their ability to resist addition reactions ** Degree of unsaturation **Saturated fat or satu ...

are possible in the third ring which is indicated here in the

structural formula The structural formula of a chemical compound is a graphic representation of the molecular structure (determined by structural chemistry methods), showing how the atoms are connected to one another. The chemical bonding within the molecule is al ...

by coloring the optionally double bonds red and blue:

Overview of simple β-carbolines

List of simple β-carbolines

A list of simple β-carbolines is tabulated by structure below. Their structures may contain the aforementioned bonds marked by red or blue.

Natural occurrence

β-Carboline

s are widespread in

s and

s. Some β-carbolines, notably tetrahydro-β-carbolines, may be formed naturally in plants and the human body with

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

and

precursors Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), hypothesized genus of fossil birds that was composed of fossilized parts of unre ...

. * Altogether, eight plant families are known to express 64 different kinds of β-carboline alkaloids. For example, the β-carbolines harmine,

, and tetrahydroharmine are components of the liana ''

'' and play a pivotal role in the pharmacology of the indigenous

psychedelic drug Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary mental states (known as psychedelic experiences or "trips") and a perceived "expansion of consciousness". Also referred to as classic halluc ...

. Moreover, the seeds of ''

'' ( Syrian Rue) contain between 0.16% and 5.9% β-carboline alkaloids (by dry weight). * A specific group of β-carboline derivatives, termed eudistomins, were extracted from ascidians (marine

tunicates Tunicates are marine invertebrates belonging to the subphylum Tunicata ( ). This grouping is part of the Chordata, a phylum which includes all animals with dorsal nerve cords and notochords (including vertebrates). The subphylum was at one time ...

of the family ''

Ascidiacea Ascidiacea, commonly known as the ascidians or sea squirts, is a paraphyletic class in the subphylum Tunicata of sac-like marine invertebrate filter feeders. Ascidians are characterized by a tough outer test or "tunic" made of the polysacchari ...

'') such as ''Ritterella sigillinoides'', ''

Lissoclinum fragile ''Lissoclinum fragile'' is a species of tunicate. This species was named by Willard G. Van Name in 1902 Events January * January 1 ** The Nurses Registration Act 1901 comes into effect in New Zealand, making it the first country ...

'' or ''Pseudodistoma aureum''. * Nostocarboline was isolated from a freshwater

cyanobacterium Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteria' ...

. * The fully

aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...

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. Smoking is another source of fully aromatic β-carbolines, with levels up to thousands of μg per smoker each day. * β-Carbolines have also been found in the

cuticle A cuticle (), or cuticula, is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non- homologous, differing in their origin, structu ...

s, causing their skin to

fluoresce Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with color ...

upon exposed to

light at certain wavelengths (e.g.

blacklight A blacklight, also called a UV-A light, Wood's lamp, or ultraviolet light, is a lamp that emits long-wave ( UV-A) ultraviolet light and very little visible light. One type of lamp has a violet filter material, either on the bulb or in a se ...

Notes

References

External links

*
TiHKAL #44

TiHKAL
in general

* {{Chemical classes of psychoactive drugs Anxiolytics Convulsants Entheogens Hallucinogens N-Monoalkyltryptamines Monoamine oxidase inhibitors GABAA receptor negative allosteric modulators Indole alkaloids Psychedelic tryptamines Tryptamine alkaloids