What Do Tryptamines Do?

You are probably familiar with the tryptamines LSD and ‘magic mushrooms,’ even if you’ve never heard them called that word. Likewise, if you were asked what do tryptamines do, you probably think you have all the answers. Yes, the predominant effect tryptamine exposure is known for is hallucinations. However, the uses of tryptamines are many and varied, and involve anything from the illicit recreational use that is glamorized in popular culture to new, innovative psychological and medicinal treatments. Another important aspect of tryptamines is that they serve important purposes both clinically and medically as neurotransmitters, neuromodulators, vasoconstrictors and vasodilators.

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Tryptamine’s Biomedical Significance

Tryptamines are found throughout the world, and there are natural and synthetic derivatives of it. Some natural sources occur in more significant quantities than others, but most of the drugs in the tryptamine category are produced in a lab setting. When produced synthetically, tryptamine is formed by the decarboxylation of L-tryptophan.

So, what is tryptamine, exactly? A tryptamine is a monoamine alkaloid with an indole ring structure inside it. The indole ring is considered the essential nucleus of complex natural products because of its important role in newly discovered drugs. Classes of natural, synthetic or semi-synthetic drugs are based on Tryptamine’s underlying structure. The following table lists some tryptamines, along with their biomedical significance.

Compound Name	Biomedical Significance
DMT (N, N-dimethyltryptamine)	Also known as the “vine of the souls,” it is a strong psychedelic compound
Serotonin (5-hydroxytryptamine, 5-HT)	CNS neurotransmitter and signaling hormones
Sumatriptan	Migraine treatment
α-methyltryptamine (V)	Antidepressant, stimulant, psychedelic drug, MAOI, and more
55-CT (5-Carboxamidotryptamine)	Vasoconstrictor and Vasodilator effect
Ondansetron (VII)	Suppresses nausea and vomiting due to cancer chemo and radiotherapy
Alosetron	Treats IBS
Tryptamine derivative of securinine (TPS)	Exhibits cytoprotective and antioxidant action
Psilocin (4-hydroxy-N,N-dimethyltryptamine)	Causes psychotropic effects that produce changes in behavior and perception
Psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine)	Causes psychotropic effects that produce changes in behavior and perception
Tryptamine based sulfonamide-compound	Has antimicrobial and antibacterial agents
Phosphorylated derivative of tryptamine	Has antioxidant properties
N-(2-(1H-Indol-3-yl)ethyl)-4-fluorobenzenesulfonamide	Has antifungal properties

 

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Neurotransmitter or Neuromodulator?

Tryptamines possess vital functions in central neurotransmission. The demonstration of specific receptors for tryptamine in the central nervous system (CNS) strongly indicates a neurotransmitter role. However, a convincing scientific argument can be made for its purpose as a modifier of central serotonin receptor systems.

There are a number of naturally derived tryptamines, chief of which is serotonin. Serotonin receptors (5H-T) are found in all animals. It is of vital importance when it comes to humans because it acts as a neurotransmitter that increases the serotonergic activity of the human brain.

In making the case that tryptamines are also neuromodulators, consider the following: Serotonin receptors modulate the release of critical signaling hormones involved in the CNS harmonization and regulation of cognition, memory, behavior and temperature regulation.

 

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Synthetic Tryptamine Therapies

Synthetic derivatives of tryptamine can help with a host of mental disorders and cognitive problems. For instance, α-methyltryptamine, a psychedelic from the tryptophan class, functions as an antidepressant, stimulant and monoamine oxidase inhibitor (MAOI). Tryptamine also has significant anti-inflammatory, antioxidant, antifungal and antibacterial activities. Relatedly, a study by the Russian Academy of Sciences indicated that Securinine-derived tryptamine has an antioxidant and chelating effect that stopped seizure activity in experimental epilepsy patients. The findings hold promise in the development of new types of neuroprotective, anticonvulsant drugs.

Natural melatonin is a hormone produced by the brain’s pineal gland that declines after the teen years, resulting in insomnia for many adults. One of the most common tryptamine treatment regimens is the use of synthetically-produced melatonin for insomnia. Other treatments by synthetic tryptamines include sumatriptan for migraine, ondansetron for alleviating the nausea and vomiting caused by certain cancer treatments and alosetron for irritable bowel syndrome (IBS).

 

Achievements as Vasodilator and Vasoconstrictor

Studies show that certain tryptamines present themselves as both a vasodilator and vasoconstrictor. Vasodilators are important in medical and clinical use because they are used to treat conditions such as hypertension, congestive heart failure and erectile dysfunction. Maintaining lower blood pressure through the use of vasodilators reduces the chance of developing other cardiac problems.

Vasoconstrictors are important for medical treatments, also. Examples include antihistamines, stimulants and amphetamines. Medicinal use for vasoconstrictors includes using them as topical decongestants and treating hypotension. They are also utilized clinically to reduce local blood flow and increase blood pressure. Vasoconstrictors are combined with local anesthetics to increase the duration of local anesthesia by working to constrict the blood vessels. The benefits of this method are that the local anesthetic agent is safely concentrated during the extended period, and the risk of hemorrhage is reduced.

 

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Review of Mechanisms Behind the Dual Functions

Researchers from the University of Engineering and Information Technology discussed the mechanisms behind how certain tryptamines act dually as both vasoconstrictors and vasodilators. They presented their findings in the review, Biomedical Significance of Tryptamine in the Journal of Pharmacovigilance. The authors also indicated that certain drugs could negate the effects during the study.

 

The authors said that,

 

“Tryptamine, a trace indirect sympathomimetic amine and subtype of vascular 5-HT-like receptors are not consistently dispersed over [the] cardiovascular system. By vasoconstriction, tryptamine enhances blood pressure because of noradrenaline discharge from sympathetic neurons.”

 

Furthermore, the authors said that tests showed that tryptamine correlates with 5-HT receptors because of its structural resemblance and produces vasoconstrictor responses that included a narrowing of the aorta. The tryptophan sumatriptan elicited a vasoconstrictor response. But, the response was limited to definite blood vessels and restricted to the cerebral vascular beds. Studies also indicated that the vasoconstrictor response could be terminated by using the following two antagonists that target the serotonin system: The antipsychotic ritanserin and the antihypertensive agent ketanserin. 

Studies show that the tryptamine analogue 5-CT (5-Carboxamidotryptamine) acted with a strong vasodilator effect on vascular smooth muscle during the study. However in certain other vascular beds, 5-CT caused vasoconstrictor responses. In different vascular regions of animal subjects, the cell surface receptors 5-HT7 interceded cases of vasodilatation.

A marked vasodilator response was indicated when “tryptamine was tested in the presence of ritanserin in mesenteric vascular beds” after an increase of perfusion pressure was applied by phenylephrine infusion.  Trace amines βphenylethylamine and tyramine demonstrated vasodilator responses under perfusion pressure akin to tryptamine because of the activation of trace amine-associated receptors. This effect is halted “by the action of L-NAME (NG-nitro-L-arginine methyl ester),” say the researchers.