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A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
2C (2C-x) is a general name for the family of psychedelic phenethylamines containing methoxy groups on the 2 and 5 positions of a benzene ring. Most of these compounds also carry lipophilic substituents at the 4 position, usually resulting in more potent and more metabolically stable and longer acting compounds. Most of the currently known 2C compounds were first synthesized by Alexander Shulgin in the 1970s and 1980s and published in his book PiHKAL. Shulgin also coined the term 2C, being an acronym for the 2 carbon atoms between the benzene ring and the amino group.
TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University. It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist for the 5-HT2A and 5-HT2C receptors with a Ki of 0.26 nM at the human 5-HT2A receptor. In drug-substitution experiments in rats, TCB-2 was found to be of similar potency to both LSD and Bromo-DragonFLY, ranking it among the most potent phenethylamine hallucinogens yet discovered. This high potency and selectivity has made TCB-2 useful for distinguishing 5-HT2A mediated responses from those produced by other similar receptors. TCB-2 has similar but not identical effects in animals to related phenethylamine hallucinogens such as DOI, and has been used for studying how the function of the 5-HT2A receptor differs from that of other serotonin receptors in a number of animal models, such as studies of cocaine addiction and neuropathic pain.
25B-NBOMe is a derivative of the phenethylamine psychedelic 2C-B, discovered in 2004 by Ralf Heim at the Free University of Berlin. It acts as a potent full agonist for the 5HT2A receptor. Duration of effects lasts about 3–10 hours, although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses. Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.
4-Substituted-2,5-dimethoxyamphetamines (DOx) is a chemical class of substituted amphetamine derivatives featuring methoxy groups at the 2- and 5- positions of the phenyl ring, and a substituent such as alkyl or halogen at the 4- position of the phenyl ring. Most compounds of this class are potent and long-lasting psychedelic drugs, and act as highly selective 5-HT2A, 5-HT2B, and 5-HT2C receptor partial agonists. A few bulkier derivatives such as DOAM have similarly high binding affinity for 5-HT2 receptors but instead act as antagonists, and so do not produce psychedelic effects though they retain amphetamine-like stimulant effects.
25I-NBF is a derivative of the phenethylamine hallucinogen 2C-I, which acts as a highly potent partial agonist for the human 5-HT2A receptor, with bias towards the β-arrestin 2 coupled signalling pathway. It has been studied in its 11C radiolabelled form as a potential ligand for mapping the distribution of 5-HT2A receptors in the brain, using positron emission tomography (PET).
Substituted tryptamines, or simply tryptamines, also known as serotonin analogues (i.e., 5-hydroxytryptamine analogues), are organic compounds which may be thought of as being derived from tryptamine itself. The molecular structures of all tryptamines contain an indole ring, joined to an amino (NH2) group via an ethyl (−CH2–CH2−) sidechain. In substituted tryptamines, the indole ring, sidechain, and/or amino group are modified by substituting another group for one of the hydrogen (H) atoms.
LPH-5 is a psychedelic discovered by Emil Marcher-Rørsted, Jesper L. Kristensen and Anders A. Jensen at Danish biopharmaceutical company Lophora. It is a conformationally-restricted derivative of the phenethylamine 2C-TFM, also a hallucinogen, and acts as a potent agonist of the 5-HT2A receptor (EC50 = 3.2 nM, Emax = 78%). It shows 10- to 100-fold selectivity for the 5-HT2A receptor over the 5-HT2B and 5-HT2C receptors and, along with related compounds like 25CN-NBOH, is said to be one of the few truly selective 5-HT2A receptor agonists. LPH-5 is expected to avoid the cardiac risks of 5-HT2B receptor activation.
CYB210010, also known as 2C-T-TFM, is a lesser-known psychedelic drug of the phenethylamine family related to compounds such as 2C-T and 2C-T-21.
2C-T-21.5 is a lesser-known psychedelic drug related to compounds such as 2C-T-21 and 2C-T-28. It was originally named by Alexander Shulgin and discussed in his book PiHKAL, but was not synthesised at that time. 2C-T-21.5 was ultimately synthesised and tested by Daniel Trachsel some years later. It has a binding affinity of 146 nM at 5-HT2A and 55 nM at 5-HT2C. It produces typical psychedelic effects, being slightly less potent but somewhat longer acting than 2C-T-2 or 2C-T-21, with an active dose of 12–30 mg, and a duration of action of 8–14 hours. Unlike 2C-T-21 it will not form the highly toxic fluoroacetate as a metabolite, instead producing the less toxic difluoroacetic acid.
ITI-1549 is a putatively non-hallucinogenic serotonin 5-HT2A receptor agonist which is under development for the treatment of mood disorders and other psychiatric disorders. In addition to acting at the serotonin 5-HT2A receptor, it is also an antagonist of the serotonin 5-HT2B receptor and an agonist of the serotonin 5-HT2C receptor. The drug's route of administration has not been specified.
CYB003, or CYB-003, also known as deuterated psilocybin analogue, is a serotonergic psychedelic related to psilocybin which is under development for the treatment of major depressive disorder, alcoholism, and other psychiatric disorders. It is taken by mouth.
CYB004, or CYB-004, also known as deuterated dimethyltryptamine (dDMT), is a serotonergic psychedelic related to dimethyltryptamine (DMT) which is under development for the treatment of generalized anxiety disorder. It is administered by inhalation or intravenous injection.
MSP-1014 is a serotonergic psychedelic which is under development for the treatment of major depressive disorder, other depressive disorders, and anxiety disorders.
BMB-202 is a serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of depressive disorders and post-traumatic stress disorder (PTSD). It is taken by mouth. However, BMB-202 has also been evaluated by injection in preclinical studies.
LPH-48 is a selective serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of alcoholism. Its route of administration has not been specified.
MYCO-005 is a serotonin 5-HT2A receptor agonist and psychedelic hallucinogen which is under development for the treatment of depressive disorders and anxiety disorders.
References
- 1 2 3 4 5 6 7 8 Cano GH, Dean J, Abreu SP, Rodríguez AH, Abbasi C, Hinson M, Lucke-Wold B (December 2022). "Key Characteristics and Development of Psychoceuticals: A Review". Int J Mol Sci. 23 (24): 15777. doi: 10.3390/ijms232415777 . PMC 9779201 . PMID 36555419.
Table 1. Biochemical structures, mechanisms, and receptor functions of twenty psychoceutical drugs.: [...] Drug Name: Phenethylamine derivative (CYB005): Chemical Structure: *. Target type: –. Method of Action: CYB005 inhibits serotonin and dopamine transporters within the synaptic cleft. [...] These drugs generally bind to CNS G-protein receptors within the 5-HT family, such as 5-HT1A, 5-HT2A, and 5-HT2B, and act agonistically [9,13–15,17,18]. Additionally, two of these, ecstasy and CYB005 (phenethylamine derivative [20]), block the reuptake of serotonin, increasing the serotonin levels within the synaptic cleft [12,21,22]. [...] According to preclinical data, CYB005, a phenethylamine derivative, aims to inhibit serotonin transporters within the synaptic cleft [20–22]. [...] Studies on [...] CYB005 [...] were not found in the literature search, so this information was obtained through the websites of their respective pharmaceutical companies. [...] Table 2. Highlights of the psychoceutical benefits.: Drug: CYB005 (Phenethylamine derivative). Benefit: Treats neuroinflammation and psychiatric conditions. [...] Three [deuterated] drugs that researchers have been working on are [...] CYB005 (for neuroinflammation). [...] Finally, CYB005 is a phenethylamine derivative currently in preclinical development [55], which has the potential to treat neuroinflammation and psychiatric conditions [20]. [...] Of the 20 drugs, [...] CYB005 [...] do not currently have completed clinical trials.
- 1 2 3 4 5 6 "CYB 005". AdisInsight. 28 October 2024. Retrieved 10 November 2024.
CYB 005 is a phenethylamine derivative is being developed by Cybin for the treatment of treatment resistant psychiatric disorders.
- 1 2 3 4 "Delving into the Latest Updates on CYB-005 with Synapse". Synapse. 1 November 2024. Retrieved 10 November 2024.
- 1 2 "Cybin Announces Grant of First U.S. Composition of Matter Patent in Support of its CYB005 Phenethylamines Program". Yahoo Finance. 24 October 2024. Retrieved 10 November 2024.
- ↑ Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, Morgan ME, Reichelt AC, Pathare P, Stang E, Palfreyman MG, Nivorozhkin A (April 2024). "Synthesis and Structure-Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT2 Receptor Agonist". J Med Chem. 67 (8): 6144–6188. doi:10.1021/acs.jmedchem.3c01961. PMID 38593423.
- ↑ Palfreyman M, Varty G, Canal C, Hartsel J, Tyagi R, Avery K, Morgan M, Mueller T, Reichelt A, Pathare P, Stang E, Nivorozhkin A (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 – P500: P405. Discovery and Preclinical Characterization of the Phenylalkylamine, CYB210010, a Potent and Long-Acting Serotonin 5-HT2A Receptor Agonist". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (299–299. doi:10.1038/s41386-023-01756-4. PMC 10729596. PMID 38040810.
- ↑ "Therapeutic phenethylamine compositions and methods of use". Google Patents. 18 August 2021. Retrieved 10 November 2024.
- ↑ Peplow M (June 2024). "Next-generation psychedelics: should new agents skip the trip?". Nat Biotechnol. 42 (6): 827–830. doi:10.1038/s41587-024-02285-1. PMID 38831049.
