Tryptoline
Chemical compound
From Wikipedia, the free encyclopedia
Tryptoline, also known as 1,2,3,4-tetrahydro-β-carboline (THβC) and tetrahydronorharmane (THN), is a natural organic derivative of β-carboline.[1] It is an alkaloid chemically related to tryptamines.[1] Derivatives of tryptoline have a variety of pharmacological properties and are known collectively as tryptolines.[2]
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| Names | |
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| Preferred IUPAC name
2,3,4,9-Tetrahydro-1H-pyrido[3,4-b]indole | |
| Other names
Noreleagnine; Tetrahydronorharman; THN; 2,3,4,9-Tetrahydro-1H-β-carboline; 1,2,3,4-Tetrahydro-β-carboline; Tetrahydro-β-carboline; THβC; THBC | |
| Identifiers | |
3D model (JSmol) |
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| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.156.194 |
PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C11H12N2 | |
| Molar mass | 172.226 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Use and effects
The properties and effects of tryptoline in humans do not appear to be known.[1]
Pharmacology
Pharmacodynamics
Tryptolines are competitive selective inhibitors of the enzyme monoamine oxidase type A (MAO-A). 5-Hydroxytryptoline and 5-methoxytryptoline are the most active monoamine oxidase inhibitors (MAOIs) with IC50 values of 500 nM and 1,500 nM, respectively.[3]
Tryptolines are also potent reuptake inhibitors of serotonin and epinephrine, with a significantly greater selectivity for serotonin.[3][4]
In-vivo formation of tryptolines has been a matter of controversy.[3][1]
Tryptoline shows weak affinity for the serotonin 5-HT1A and 5-HT2A receptors (Ki = 2,510 nM and 3,900 nM, respectively).[5] However, it showed a high affinity (Ki) of 28 nM against tryptamine-labeled binding sites, whereas affinity for serotonin- and spiperone-labeled sites were much lower (Ki = 6,030 nM and 12,030 nM, respectively).[6][7] The drug shows substantially lower affinity for serotonin receptors than tryptamine.[6][7] Tryptoline is 60-fold more potent in terms of tryptamine binding site interaction than its serotonin reuptake inhibition.[7] The drug is inactive as an agonist of the serotonin 5-HT2B receptor in the rat fundus stomach strip (KB = >3,000 nM).[8]
Tryptoline is known to produce various behavioral effects in animals, including analgesia, hypothermia, and hypophagia, as well as antidopaminergic-like reversal of behavioral effects of apomorphine such as hyperlocomotion.[7][9]
Chemistry
Derivatives
Tryptoline derivatives have been found to interact with serotonin receptors, such as the serotonin 5-HT1A and 5-HT2 receptors.[5][10][7][6] A couple of notable derivatives, 1-ethyl-6-hydroxytryptoline and 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline, are potent and high-efficacy agonists of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A receptor.[10]