beta-Carboline

β-Carboline alkaloids are widespread in plants and animals, and frequently act as GABA_A inverse agonists. As components of the liana Banisteriopsis caapi, the β-carbolines harmine, harmaline, and tetrahydroharmine play a pivotal role in the pharmacology of the indigenous psychedelic drug ayahuasca by preventing the breakdown of dimethyltryptamine in the gut by reversibly inhibiting monoamine oxidase, thus making it psychoactive upon oral administration. Some β-carbolines, notably tryptoline and pinoline, may be formed naturally in the human body. The latter is possibly implicated along with melatonin in the role of the pineal gland in regulating the sleep-wake cycle. β-carboline is a GABA_A benzodiazepine site inverse agonist and can therefore have convulsive, anxiogenic and memory enhancing effects.[2] 3-hydroxymethyl-beta-carboline blocks the sleep-promoting effect of flurazepam in rodents, and by itself can decrease sleep in a dose-dependent manner.[3] 9-Methyl-β-carbolines appear to induce DNA damage when exposed to ultraviolet light.[4]

β-Carboline belongs to the group of indole alkaloids and consist of pyridine ring that is fused to an indole skeleton.[5] 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.[6] Different levels of saturation are possible in the third ring, which is indicated here in the structural formula by colouring the optionally double bonds red and blue:

Substituted beta-carbolines (structural formula)

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

Short Name	Red Bond	Blue Bond	R1	R6	R7	R9	Structure
β-Carboline	×	×	H	H	H	H
Tryptoline			H	H	H	H
Pinoline			H	OCH3	H	H
Harmane	×	×	CH3	H	H	H
Harmine	×	×	CH3	H	OCH3	H
Harmaline	×		CH3	H	OCH3	H
Tetrahydroharmine			CH3	H	OCH3	H
9-Methyl-β-carboline	×	×	H	H	H	CH3

A Paruroctonus scorpion fluorescing under a blacklight

Eight plant families are known to express 64 different kinds of β-carboline alkaloids. By dry weight, the seeds of Peganum harmala (Syrian Rue) contain between 0.16%[7] and 5.9%[8] β-carboline alkaloids.

As a result of the presence of β-carbolines in the cuticle of scorpions, their skin is known to fluoresce when exposed to certain wavelengths of ultraviolet light such as that produced by a blacklight.[9]

A group of β-carboline derivatives, termed eudistomins were extracted from ascidians (marine tunicates of the family Ascidiacea), like Ritterella sigillinoides,[10] Lissoclinum fragile [11] or Pseudodistoma aureum.[12] Nostocarboline was isolated from freshwater cyanobacterium.

β-carboline derivatives are known to induce the production of secondary metabolite in various soil dwelling “Streptomyces” species.[13][14] Defined as biomediator, these molecules are known to enhance the expression of secondary metabolite biosynthetic genes by binding to large ATP-binding regulator of the LuxR family.

• Harmala alkaloid
• Tryptamine
• Gamma-carboline

• Beta-Carbolines at the US National Library of Medicine Medical Subject Headings (MeSH)
• TiHKAL #44
• TiHKAL in general
• Beta-carbolines in coffee
• Farzin D, Mansouri N (July 2006). "Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test". Eur Neuropsychopharmacol. 16 (5): 324–8. doi:10.1016/j.euroneuro.2005.08.005. PMID 16183262.