5-Chlorotryptamine

5-Chlorotryptamine
Clinical data
Other names5-Chloro-T; 5-Cl-T; 5-ClT; PAL-441; PAL441
Drug classSerotonin receptor modulator; Serotonin 5-HT2A receptor agonist; Serotonin releasing agent
ATC code
  • None
Identifiers
  • 2-(5-chloro-1H-indol-3-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.021.077 Edit this at Wikidata
Chemical and physical data
FormulaC10H11ClN2
Molar mass194.66 g·mol−1
3D model (JSmol)
  • C1=CC2=C(C=C1Cl)C(=CN2)CCN
  • InChI=1S/C10H11ClN2/c11-8-1-2-10-9(5-8)7(3-4-12)6-13-10/h1-2,5-6,13H,3-4,12H2
  • Key:FVQKQPVVCKOWLM-UHFFFAOYSA-N

5-Chlorotryptamine (5-Cl-T; developmental code name PAL-441) is a serotonin receptor modulator and monoamine releasing agent of the tryptamine family. It is the 5-chloro derivative of tryptamine.

The drug shows affinity for the serotonin 5-HT1A, 5-HT2A, 5-HT6, and 5-HT7 receptors (Ki = 5.5–16 nM, 317–889 nM, 38 nM, and 16 nM, respectively). It acts as a potent agonist of the serotonin 5-HT1A receptor (EC50Tooltip half-maximal effective concentration = 3,846 nM) and of the 5-HT2A receptor (EC50 = 4.11–145 nM; EmaxTooltip maximal efficacy = 109%). In addition, 5-chlorotryptamine is a serotonin releasing agent (SRA), with EC50 values for induction of monoamine release of 19.1 nM for serotonin, 476 nM for dopamine, and >10,000 nM for norepinephrine in rat brain synaptosomes. Similarly to tryptamine and other simple amine-unsubstituted tryptamines, 5-chlorotryptamine was ineffective in producing the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.

Tryptamines without substitutions at the amine or alpha carbon, such as tryptamine, serotonin (5-hydroxytryptamine; 5-HT), and 5-methoxytryptamine (5-MeO-T), are known to be very rapidly metabolized and thereby inactivated by monoamine oxidase A (MAO-A) in vivo and to have very short elimination half-lives. However, given intravenously at sufficiently high doses, tryptamine is still known to be able to produce weak and short-lived psychoactive effects in humans.

The chemical synthesis of 5-chlorotryptamine has been described.

5-Chlorotryptamine was first described in the scientific literature by 1959.

See also

References

  1. 1 2 3 4 5 6 Blough BE, Landavazo A, Partilla JS, Decker AM, Page KM, Baumann MH, et al. (October 2014). "Alpha-ethyltryptamines as dual dopamine-serotonin releasers". Bioorganic & Medicinal Chemistry Letters. 24 (19): 4754–4758. doi:10.1016/j.bmcl.2014.07.062. PMC 4211607. PMID 25193229.
  2. ↑ Hogendorf AS, Hogendorf A, Kurczab R, Satała G, Lenda T, Walczak M, et al. (May 2017). "Low-basicity 5-HT7 Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol". Scientific Reports. 7 (1) 1444. doi:10.1038/s41598-017-00822-4. PMC 5431432. PMID 28473721.
  3. 1 2 3 Chen X, Li J, Yu L, Maule F, Chang L, Gallant JA, et al. (October 2023). "A cane toad (Rhinella marina) N-methyltransferase converts primary indolethylamines to tertiary psychedelic amines". The Journal of Biological Chemistry. 299 (10) 105231. doi:10.1016/j.jbc.2023.105231. PMC 10570959. PMID 37690691.
  4. 1 2 3 Chen X, Li J, Yu L, Dhananjaya D, Maule F, Cook S, et al. (10 March 2023), Bioproduction platform using a novel cane toad (Rhinella marina) N-methyltransferase for psychedelic-inspired drug discovery (PDF), doi:10.21203/rs.3.rs-2667175/v1, retrieved 17 March 2025
  5. ↑ Jones RS (1982). "Tryptamine: a neuromodulator or neurotransmitter in mammalian brain?". Progress in Neurobiology. 19 (1–2): 117–139. doi:10.1016/0301-0082(82)90023-5. PMID 6131482.
  6. 1 2 Shulgin A (1997). Tihkal: The Continuation. Transform Press. #53. T. ISBN 978-0-9630096-9-2. Retrieved 17 August 2024. (with 250 mg, intravenously) "Tryptamine was infused intravenously over a period of up to 7.5 minutes. Physical changes included an increases in blood pressure, in the amplitude of the patellar reflex, and in pupillary diameter. The subjective changes are not unlike those seen with small doses of LSD. A point-by-point comparison between the tryptamine and LSD syndromes reveals a close similarity which is consistent with the hypothesis that tryptamine and LSD have a common mode of action."
  7. ↑ Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X.
  8. ↑ Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524.
  9. ↑ Prozialeck WC, Vogel WH (February 1979). "MAO inhibition and the effects of centrally administered LSD, serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats". Psychopharmacology. 60 (3): 309–310. doi:10.1007/BF00426673. PMID 108709. In contrast, MAO inhibition greatly increased brain levels of 5-HT and 5-MT (Prozialeck and Vogel, 1978). For instance, clorgyline and deprenyl increased brain levels of 5-HT 8.5-fold and 4.4-fold and of 5-MT 20-fold and 5-fold, respectively.
  10. ↑ Boess FG, Martin IL (1994). "Molecular biology of 5-HT receptors". Neuropharmacology. 33 (3–4): 275–317. doi:10.1016/0028-3908(94)90059-0. PMID 7984267.
  11. 1 2 Martin WR, Sloan JW (1970). "Effects of infused tryptamine in man". Psychopharmacologia. 18 (3): 231–237. doi:10.1007/BF00412669. PMID 4922520.
  12. ↑ Martin WR, Sloan JW (1977). "Pharmacology and Classification of LSD-like Hallucinogens". Drug Addiction II. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 305–368. doi:10.1007/978-3-642-66709-1_3. ISBN 978-3-642-66711-4. MARTIN and SLOAN (1970) found that intravenously infused tryptamine increased blood pressure, dilated pupils, enhanced the patellar reflex, and produced perceptual distortions. [...] Tryptamine, but not DMT, increases locomotor activity in the mouse, while both antagonize reserpine depression (V ANE et al., 1961). [...] In the rat, tryptamine causes backward locomotion, Straub tail, bradypnea and dyspnea, and clonic convulsions (TEDESCHI et al., 1959). [...] Tryptamine produces a variety of changes in the cat causing signs of sympathetic activation including mydriasis, retraction of nictitating membrane, piloerection, motor signs such as extension of limbs and convulsions and affective changes such as hissing and snarling (LAIDLAW, 1912). [...]
  13. ↑ Vane JR (March 1959). "The relative activities of some tryptamine analogues on the isolated rat stomach strip preparation". British Journal of Pharmacology and Chemotherapy. 14 (1): 87–98. doi:10.1111/j.1476-5381.1959.tb00933.x. PMC 1481817. PMID 13651584.
  14. ↑ Gupta SP, Singh P, Bindal MC (1 December 1983). "QSAR studies on hallucinogens". Chemical Reviews. 83 (6): 633–649. doi:10.1021/cr00058a003. ISSN 0009-2665.