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Product name: Bufotenin
Synonym name: Dimethylserotonin; Mappin; Mappine; N,N-Dimethyl-5-hydroxytryptamine; N,N-Dimethylserotonin
Catalogue No.: BP4265
Cas No.: 487-93-4
Formula: C12H16N2O
Mol Weight: 204.273
Botanical Source: Bufonis Venenum
Type of Compound: Alkaloids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
Description:
Bufotenine may have hallucinogenic potential, the presence and levels of bufotenine might be useful and important markers of some psychiatric disorders. Bufotenine is able to block rabies virus infection in BHK-21 cells.
References:
J Psychoactive Drugs. 2000 Jul-Sep;32(3):321-31.
Bufotenine: toward an understanding of possible psychoactive mechanisms.
METHODS AND RESULTS:
A review of the neuropharmacology of the alleged hallucinogen Bufotenine is presented, including recent experimental results showing activity similar to LSD and other known hallucinogens (psilocin and 5-MeO-DMT) at the purported hallucinogenic serotonin (5-HT) receptors, 5-HT2A and 5-HT2C. In addition, current reports of computer modeling of the receptors and ligand binding sites give evidence of Bufotenine's ability to bind and activate these receptors. While binding and activation of the purported hallucinogenic receptors are not the full extent of the hallucinogenic signature, this evidence shows support for the rationale that the reported lack of the drug's classic hallucinogenic response in human experiments is due to poor ability to cross the blood brain barrier (BBB), not lack of activation of the appropriate brain receptors. Further evidence is reviewed that in some physiological states, some drugs with characteristics similar to Bufotenine which do not normally cross the BBB, cross it and enter the brain.
CONCLUSIONS:
While direct human experimental evidence of Bufotenine's hallucinogenic activity seems lacking, the above combined factors are considered, and possible explanations of Bufotenine's reported psychoactivity are suggested. Additionally, updated experimental models testing the possible nature of Bufotenine's hallucinogenic potential are proposed.
J Venom Anim Toxins Incl Trop Dis. 2014 Oct 13;20(1):45.
Bufotenine is able to block rabies virus infection in BHK-21 cells.
Rabies is a fatal zoonotic neglected disease that occurs in more than 150 countries, and kills more than 55.000 people every year. It is caused by an enveloped single stranded RNA virus that affects the central nervous system, through an infection initiated by the muscular nicotinic acetylcholine receptor, according to many authors. Alkaloids, such as acetylcholine, are widespread molecules in nature. They are present in numerous biological fluids, including the skin secretion of many amphibians, in which they act (together with proteins, peptides and steroids) as protection agents against predators and/or microorganisms. Among those amphibians that are rich in alkaloids, there is the genus Rhinella.
METHODS AND RESULTS:
Bufotenine was isolated from Rhinela jimi skin secretion after a liquid-liquid partition (H2O:CH2Cl2) and reversed phase high-performance liquid chromatography analyses (RP-HPLC). Bufoteninewas also extracted from seeds of Anadenanthera colubrina in acetone solution and purified by RP-HPLC, as well. Structural characterization was performed by mass spectrometry and nuclear magnetic resonance analyses. Cytotoxic tests of Bufotenine were performed over baby hamster kidney (BHK-21) cells using MTT test. For the antiviral activity, Rabies virus strain Pasteur vaccine (PV) was used on fluorescence inhibition test and fluorescent foci inhibition test, with both simultaneous and time course treatment of the cells with the virus and Bufotenine. In the present work we describe the effects of Bufotenine, obtained either from toads or plants, that can inhibit the penetration of rabies virus in mammalian cells through an apparent competitive mechanism by the nicotinic acetylcholine receptor. Moreover, this inhibition was dose- and time-dependent, pointing out to a specific mechanism of action.
CONCLUSIONS:
This work do not present or propose Bufotenine as a drug for the treatment of rabies due to the hallucinogen and psychotropic effects of the molecule. However, continued studies in the elucidation of the antiviral mechanism of this molecule, may lead to the choice or development of a tryptamine analogue presenting potential clinical use.
Neuroreport. 1995 Nov 27;6(17):2378-80.
Bufotenine reconsidered as a diagnostic indicator of psychiatric disorders.
We have analyzed products of the serotonin-degradative pathway, in which both N-methylserotonin and Bufotenine are formed in urine specimens of products with psychiatric disorders by three-dimensional HPLC with electrochemical detection.
METHODS AND RESULTS:
Bufotenine was detected in urine from all autistic patients with mental retardation and epilepsy (n = 18) and many autistic patients (32/47) with mental retardation. Bufotenine was detected in the urine of 15 of 18 patients with depression. Thirteen of 15 schizophrenic patients were also positive for Bufotenine. N-methylserotonin was also detected in some cases of each disorder. Only two of 200 urine specimens from healthy controls were positive for Bufotenine.
CONCLUSIONS:
Thus, the presence and levels of Bufotenine might be useful and important markers of some psychiatric disorders.
HPLC of Bufotenin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
39.2600
2.0899
.1152
.9891
1.0133
15.1866
High
30.6047
2.1247
No
Yes
No
No
Yes
Yes
0.6
No
No
Yes
No
Bufotenin (CAS number: 487-93-4) is a naturally occurring tryptamine alkaloid, structurally a five-position hydroxyl derivative of N,N-dimethyltryptamine. As a natural compound with significant hallucinogenic activity, serotonin is found in various amphibians, fungi, and certain plants. In recent years, with the deepening of research on neuropsychiatric diseases, especially the high incidence of mood disorders such as depression, serotonin, due to its unique pharmacological activity and high blood-brain barrier penetration ability, has gradually become a research hotspot in the fields of natural product pharmacology and neuropsychiatric drug development. This paper will systematically review the chemical structure and physicochemical properties of serotonin, its natural sources and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and explore its clinical application prospects in neuropsychiatric diseases such as depression.
The molecular formula of toad serotonin is C12H16N2O, with a molecular weight of 204.2730. Its chemical structure is based on the tryptamine skeleton, and the introduction of the 5-position hydroxyl group gives it unique chemical and biological properties. Structurally, serotonin is a tertiary amine, and its N,N-dimethyl substituents enhance the molecule's lipid solubility and brain penetration. In terms of physicochemical properties, serotonin has a LogP value of 2.0899, indicating moderate lipid solubility that facilitates blood-brain barrier penetration. The polar surface area (TPSA) was 39.26 Ų, and the lower polar surface area further supported its good distribution of brain tissue. Water solubility is 0.9891, indicating a certain solubility under physiological conditions, facilitating absorption and distribution in the body. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames mutagenic test scored 0.6, indicating a low genotoxicity risk and meeting safety requirements for drug development.
Toad tryptamine was first isolated and identified from toad skin secretions, especially abundant in the secretions of toad animals such as the genus Bufo. Additionally, certain fungi and plants such as certain legumes have found the compound in the seeds of certain legumes. Traditionally, serotonin extraction has mostly relied on organic solvent extraction and bind liquid-to-liquid distribution. The specific steps include: drying and crushing toad skin or related biological materials, then extracting with methanol or ethanol, and then enriching tryptamine alkaloids through acid-base adjustment. Further liquid-liquid extraction (such as chloroform or ethyl acetate) is used to separate impurities, followed by purification and qualitative analysis using high-performance liquid chromatography (HPLC) or gas chromatography-mass spectrometry (GC-MS) techniques. Modern extraction technologies such as ultrasonic-assisted extraction and solid-phase extraction have gradually been applied to efficient extraction of serotonin, improving extraction rates and purity.
As a natural hallucinogen, serotonin mainly focuses its pharmacological effects on the central nervous system. In vitro and in vivo studies have shown that serotonin can regulate multiple neurotransmitter systems, especially the activity of the 5-hydroxytryptamine (5-HT) receptor subtype, exhibiting neuromodulatory functions similar to those of classic hallucinogens. Its hallucinogenic effects are closely related to the excitation of 5-HT2A receptors, and it also has certain affinity for 5-HT1A and 5-HT2C receptors, affecting neuronal excitability and neural network function.
In depression models, serotonin exhibits antidepressant-like activity. In animal behavioral experiments (such as forced swimming and tail suspension tests), serotonin can significantly reduce depressive-like behaviors, suggesting potential antidepressant effects. Its antidepressant mechanisms may be closely related to regulating signaling pathways related to neuroinflammation, oxidative stress, and neuroplasticity. Additionally, serotonin inhibits the expression of the neuroinflammatory factor TNF-α, demonstrating certain neuroprotective potential.
The molecular mechanism of serotonin involves multiple targets and multiple pathways of regulation, mainly including the following aspects:
Tryptamine receptor regulation
As a tryptamine derivative, toad serotonin can bind to various 5-HT receptor subtypes, especially the 5-HT2A receptor (HTR2A), which exerts stimulating effects, regulating neurotransmitter release and neuronal excitability, and affecting mood and cognitive function.
Immune regulation and suppression of neuroinflammation
By inhibiting tumor necrosis factor (TNF) and related inflammatory pathways, serotonin reduces neuroinflammatory responses and improves the pathological state of neuroinflammation associated with depression.
Oxidative stress and cell protection
Toad serotonin can activate the nuclear factor red 2-related factor 2 (NFE2L2) signaling pathway, enhancing cellular antioxidant capacity, reducing oxidative damage, and protecting neuronal function.
Regulation of neurotransmitter metabolic enzymes
By regulating the activities of indole amine 2,3-bioxygenase (IDO1), monoamine oxidase A (MAOA), and monoamine oxidase B (MAOB), serotonin affects the metabolic balance of tryptamine neurotransmitters and promotes neurotransmitter homeostasis.
Neural signal transduction and plasticity
Toad serotonin can regulate the mitogen-activated protein kinase 1 (MAPK1) signaling pathway, promoting neuronal plasticity and survival, and helping to repair depression-related neural network abnormalities.
Other targets
These include nicotinic acetylcholine receptor α7 subtype (CHRNA7), phosphodiesterase 4D (PDE4D), and estrogen receptor α (ESR1), which are involved in multiple mechanisms of neural regulation, cognitive function, and emotional stability.
In summary, serotonin regulates the neurotransmitter system, neuroinflammation, and oxidative stress through multi-target synergy, exerting its antidepressant and neuroprotective effects.
The druggability parameters of serotonin indicate that it has good potential for drug development. The molecular weight of 204.2730 complies with the Lipinski rule, and the LogP value of 2.0899 indicates moderate lipid solubility, which is beneficial for oral absorption and blood-brain barrier penetration. The TPSA value of 39.26 Ų is lower than 90 Ų, further supporting its excellent brain tissue distribution capacity. Water solubility is close to 1, ensuring its proper solubility in the body.
High blood-brain barrier penetration is a key advantage of serotonin as a central nervous system drug, ensuring it reaches an effective concentration in the brain. The hERG channel inhibition test was negative, indicating low potential toxicity to cardiac electrophysiology and good safety. Ames test results showed that it carries a low genotoxicity risk and meets drug safety requirements.
Pharmacokinetics, existing studies show that serotonin is well absorbed orally and widely distributed in the body, especially enriched in brain tissue. Its metabolism is mainly through the liver's tryptamine metabolic enzyme system, producing various metabolic products, some of which may be biologically active. The main excretion route is urine. Its half-life is moderate, making it suitable for dose adjustment and dosing regimen design.
As a natural tryptamine alkaloid, serotonin demonstrates its potential application value in the treatment of depression and related neuropsychiatric disorders due to its unique neuroregulatory mechanism and good druggability. Currently, antidepressants suffer from slow onset, significant side effects, and drug resistance. Serotonin regulates neurotransmitter metabolism, neuroinflammation, and oxidative stress through multiple targets, potentially offering new therapeutic strategies.
Future clinical research should focus on safety evaluation, dose optimization, and long-term efficacy monitoring of serotonin. Combined with modern drug delivery systems, such as nanocarriers and targeted drug delivery technologies, its bioavailability and targeting are expected to be further enhanced. In addition, the potential therapeutic effects of serotonin in cognitive impairment, anxiety disorders, and neurodegenerative diseases are also worth further exploration.
With advances in molecular biology and pharmacological techniques, the mechanism of serotonin's action will be further elucidated, providing a solid foundation for its clinical translation. At the same time, structural modification and derivative development may also bring superior efficacy and safety, making it an important candidate for next-generation neuropsychiatric drugs.
In summary, as a natural tryptamine alkaloid with a unique chemical structure and multi-target mechanism, serotonin shows broad application prospects in the treatment of central nervous system diseases, especially depression. Its excellent druggability parameters and safety evaluation lay the foundation for drug development. In the future, through in-depth pharmacological mechanism research, optimized extraction and synthesis processes, and improved preclinical and clinical studies, it is expected that serotonin can be translated into clinical practice, enriching treatment options for neuropsychiatric diseases and benefiting patients.
Shenshuai
Wenjing
Hedandan
