Tryptamine

Tryptamine, also known as 2-(3-indolyl)ethylamine, 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 first one being the heterocyclic nitrogen). The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others. Tryptamine has been shown to activate serotonin receptors and trace amine-associated receptors expressed in the mammalian brain, and regulates the activity of dopaminergic, serotonergic and glutamatergic systems. In the human gut, bacteria convert dietary tryptophan to tryptamine, which activates 5-HT 4 receptors and regulates gastrointestinal motility. Multiple tryptamine-derived drugs have been developed to treat migraines, while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders.

Tryptamine, also known as 2-(3-indolyl)ethylamine, 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 first one being the heterocyclic nitrogen). The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others. Tryptamine has been shown to activate serotonin receptors and trace amine-associated receptors expressed in the mammalian brain, and regulates the activity of dopaminergic, serotonergic and glutamatergic systems. In the human gut, bacteria convert dietary tryptophan to tryptamine, which activates 5-HT 4 receptors and regulates gastrointestinal motility. Multiple tryptamine-derived drugs have been developed to treat migraines, while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders. Tryptamine is known to act as a serotonin receptor agonist, although its potency is limited by rapid inactivation by monoamine oxidases. It has specifically been found to act as a full agonist of the serotonin 5-HT 2A receptor ( = 7.36 ± 0.56 nM; E max = 104 ± 4%). Tryptamine was of much lower potency in stimulating the 5-HT 2A receptor β-arrestin pathway ( = 3,485 ± 234 nM; E max = 108 ± 16%). In contrast to the 5-HT 2A receptor, tryptamine was found to be inactive at the serotonin 5-HT 1A receptor. Tryptamine has been found to act as a monoamine releasing agent (MRA). It is a releaser of serotonin, dopamine, and norepinephrine, in that order of potency ( = 32.6 nM, 164 nM, and 716 nM, respectively). That is, it acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA). ===Other actions=== Tryptamine has been found to act as a potent agonist of the GPR139 and to be involved in sleep regulation. ===Effects in animals and humans=== In a published clinical study, tryptamine, at a total dose of 23 to 277 mg by intravenous infusion, produced hallucinogenic effects or perceptual disturbances similar to those of small doses of lysergic acid diethylamide (LSD). It also produced other LSD-like effects, including pupil dilation, increased blood pressure, and increased force of the patellar reflex. Tryptamine produced side effects including nausea, vomiting, dizziness, tingling sensations, sweating, and bodily heaviness among others as well. Conversely, there were no changes in heart rate or respiratory rate. The onset of the effects was rapid and the duration was very short. This can be attributed to the very rapid metabolism of tryptamine by monoamine oxidase (MAO) and its very short elimination half-life. In animals, tryptamine, alone and/or in combination with a monoamine oxidase inhibitor (MAOI), produces behavioral changes such as hyperlocomotion and reversal of reserpine-induced behavioral depression. In addition, it produces effects like hyperthermia, tachycardia, myoclonus, and seizures or convulsions, among others. Findings on tryptamine and the head-twitch response in rodents have been mixed, with some studies reporting no effect, some studies reporting induction of head twitches by tryptamine, and others reporting that tryptamine actually antagonized 5-hydroxytryptophan (5-HTP)-induced head twitches. Another study found that combination of tryptamine with an MAOI dose-dependently produced head twitches. Head twitches in rodents are a behavioral proxy of psychedelic-like effects. Many of the effects of tryptamine can be reversed by serotonin receptor antagonists like metergoline, metitepine (methiothepin), and cyproheptadine. Conversely, the effects of tryptamine in animals are profoundly augmented by MAOIs due to inhibition of its metabolism. Tryptamine seems to also elevate prolactin and cortisol levels in animals and/or humans. The values of tryptamine in animals include 100 mg/kg i.p. in mice, 500 mg/kg s.c. in mice, and 223 mg/kg i.p. in rats. ==Pharmacokinetics== Tryptamine produced endogenously or administered peripherally is readily able to cross the blood–brain barrier and enter the central nervous system. This is in contrast to serotonin, which is peripherally selective. However, it has been reported that tryptamine also shows partial peripheral selectivity. Tryptamine is metabolized by monoamine oxidase (MAO) to form indole-3-acetic acid (IAA). Its metabolism is described as extremely rapid and its elimination half-life and duration as very short. In addition, its duration is described as shorter than that of dimethyltryptamine (DMT). Brain tryptamine levels are increased up to 300-fold by MAOIs in animals. In addition, the effects of exogenous tryptamine are strongly augmented by monoamine oxidase inhibitors (MAOIs). Tryptamine is excreted in urine and its rate of urinary excretion has been reported to be pH-dependent. ==Chemistry== Tryptamine is a substituted tryptamine derivative and trace amine and is structurally related to the amino acid tryptophan. ===Properties=== The experimental log P of tryptamine is 1.55. ===Synthesis=== The chemical synthesis of tryptamine has been described. ===Analogues and derivatives=== The endogenous monoamine neurotransmitters serotonin (5-hydroxytryptamine or 5-HT) and melatonin (5-methoxy-N-acetyltryptamine), as well as trace amines like N-methyltryptamine (NMT), dimethyltryptamine (DMT), and bufotenin (N,N-dimethylserotonin), are derivatives of tryptamine. A variety of drugs, including both naturally occurring and pharmaceutical substances, are derivatives of tryptamine. These include the tryptamine psychedelics like psilocybin, psilocin, DMT, and 5-MeO-DMT; tryptamine stimulants, entactogens, psychedelics, and/or antidepressants like α-methyltryptamine (αMT) and α-ethyltryptamine (αET); triptan antimigraine agents like sumatriptan; certain antipsychotics like oxypertine; and the sleep aid melatonin. Various other drugs, including ergolines and lysergamides like the psychedelic lysergic acid diethylamide (LSD), the antimigraine agents ergotamine, dihydroergotamine, and methysergide, and the antiparkinsonian agents bromocriptine, cabergoline, lisuride, and pergolide; β-carbolines like harmine (some of which are monoamine oxidase inhibitors (MAOIs)); Iboga alkaloids like the hallucinogen ibogaine; yohimbans like the α 2 blocker yohimbine; antipsychotics like ciclindole and flucindole; and the MAOI antidepressant metralindole, can all be thought of as cyclized tryptamine derivatives. Deuterated isotopologues of tryptamine include α,α-dideuterotryptamine and β,β-dideuterotryptamine, among others. A notable prodrug of tryptamine with sustained effects is N-(2-cyanoethyl)tryptamine (CE-T). Drugs very closely related to tryptamines, but technically not tryptamines themselves, include certain triptans like avitriptan and naratriptan; the antipsychotics sertindole and tepirindole; and the MAOI antidepressants pirlindole and tetrindole. ==History== Tryptamine, referred to by the name 3-β-aminoethylindole, was first synthesized by Arthur James Ewins and Patrick Laidlaw in 1910. Subsequently, they referred to it by the name indolethylamine in 1912 and 1913. The name tryptamine first emerged by at least 1918. Following tryptamine's synthesis, N-methylated tryptamines like N-methyltryptamine (NMT) and dimethyltryptamine (DMT) were synthesized by Richard Manske in 1931. Subsequently, the chemical structure of serotonin (5-hydroxytryptamine; 5-HT) was identified—and hence serotonin was first "truly" discovered (having been isolated earlier in the 1930s)—by Maurice M. Rapport in 1949. The structural similarity between serotonin and the psychedelic drug LSD, a lysergamide and cyclized tryptamine that contains tryptamine within its structure, was noticed and described by Dilworth Wayne Woolley and Elliott Shaw in 1954. The hallucinogenic effects of simple tryptamines themselves were not discovered until those of bufotenin and DMT were elucidated in 1955 and 1956, for instance by Stephen Szára, soon after their first isolation from hallucinogenic snuffs. The psychedelic effects of tryptamine itself in humans were first reported by W. R. Martin and J. W. Sloan in 1970. Tryptamine - TiHKAL - Isomer Design

Text derived from https://en.wikipedia.org/w/index.php?oldid=1369726329 under CC BY-SA 4.0; modifications have been made.