Tryptamine

For a list of plants, fungi and animals containing tryptamines, see List of psychoactive plants and List of naturally occurring tryptamines. Mammalian brain Endogenous levels of tryptamine in the mammalian brain are less than 100 ng per gram of tissue. Mammalian gut microbiome Tryptamine is relatively abundant in the gut and feces of humans and rodents. Commensal bacteria, including Ruminococcus gnavus and Clostridium sporogenes in the gastrointestinal tract, possess the enzyme tryptophan decarboxylase, which aids in the conversion of dietary tryptophan to tryptamine. Tryptamine is a ligand for gut epithelial serotonin type 4 (5-HT4) receptors and regulates gastrointestinal electrolyte balance through colonic secretions. == Metabolism ==

Biosynthesis To yield tryptamine in vivo, tryptophan decarboxylase removes the carboxylic acid group on the α-carbon of tryptophan. Catabolism Monoamine oxidases A and B are the primary enzymes involved in tryptamine metabolism to produce indole-3-acetaldehyde, however it is unclear which isoform is specific to tryptamine degradation. Figure == Biological activity ==

Serotonin receptor agonist 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-HT2A receptor ( = 7.36 ± 0.56nM; Emax = 104 ± 4%). Monoamine releasing agent 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 ( = 32.6nM, 164nM, and 716nM, respectively). That is, it enhances the action potential-mediated release of these monoamine neurotransmitters. Synthetic and more potent MAEs like benzofuranylpropylaminopentane (BPAP) and indolylpropylaminopentane (IPAP) have been derived from tryptamine. TAAR1 agonist Tryptamine is an agonist of the trace amine-associated receptor 1 (TAAR1). It is a potent TAAR1 full agonist in rats, a weak TAAR1 full agonist in mice, and a very weak TAAR1 partial agonist in humans. The TAAR1 is a stimulatory G protein-coupled receptor (GPCR) that is weakly expressed in the intracellular compartment of both pre- and postsynaptic neurons. TAAR1 agonists are under investigation as a novel treatment for neuropsychiatric conditions like schizophrenia, drug addiction, and depression. It also produced other LSD-like effects, including pupil dilation, increased blood pressure, and increased force of the patellar reflex. 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 100mg/kg i.p. in mice, 500mg/kg s.c. in mice, and 223mg/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. ==Chemistry==

Tryptamine is a substituted tryptamine derivative and trace amine and is structurally related to the amino acid tryptophan. Synthesis The chemical synthesis of tryptamine has been described. 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. == See also ==