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Pellotine

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Pellotine
BERJAYA
BERJAYA
Clinical data
Other namesPellotin; Peyotline; Peyotlin; N-Methylanhalonidine; 8-Hydroxy-6,7-dimethoxy-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline; 8-Hydroxy-6,7-dimethoxy-1,2-dimethyl-THIQ
Routes of
administration		Oral, subcutaneous injection[1]
Drug classSerotonin 5-HT6 receptor weak partial agonist; Serotonin 5-HT7 receptor inverse agonist; Serotonin 5-HT1D receptor ligand; Sedative; Hypnotic
ATC code
  • None
Identifiers
  • 6,7-dimethoxy-1,2-dimethyl-3,4-dihydro-1H-isoquinolin-8-ol
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC13H19NO3
Molar mass237.299 g·mol−1
3D model (JSmol)
Melting point110 to 113 °C (230 to 235 °F)
  • CC1C2=C(C(=C(C=C2CCN1C)OC)OC)O
  • InChI=1S/C13H19NO3/c1-8-11-9(5-6-14(8)2)7-10(16-3)13(17-4)12(11)15/h7-8,15H,5-6H2,1-4H3
  • Key:NKHMWHLJHODBEP-UHFFFAOYSA-N

Pellotine, also known as peyotline or N-methylanhalonidine, is a tetrahydroisoquinoline alkaloid found in Lophophora species, in particular Lophophora diffusa (false peyote) and to a much lesser extent Lophophora williamsii (peyote).[2][3][4][5][6][4] It produces sedative and hypnotic effects and may contribute to the non-hallucinogenic effects of peyote.[5][7] The drug was once marketed for medical use as a hypnotic in the 1890s, but was abandoned in favor of cheaper barbiturates in the 1900s.[3][5][8] Pellotine has also been sold online on chemical trading platforms in modern times.[8]

Use and effects

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Pellotine has been studied in humans and found to produce hypnotic effects in clinical studies.[1][5][3] When injected subcutaneously to humans, participants have reported drowsiness and a desire not to exert any physical or mental effort.[7][5][9] It is also reported to lower blood pressure and heart rate.[7] Pellotine produced no hallucinogenic effects in humans at doses of up to 240 mg.[2][9][10] However, it has been reported to have a calming or sedative effect instead.[9][10] On the other hand, one single study reported that pellotine produced hallucinations at a dose of 300 mg.[11][2][12]

Side effects

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Side effects of pellotine include dizziness, nausea, vertigo, and vomiting.[5]

Pharmacology

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Pharmacodynamics

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Pellotine has been identified as a selective and potent serotonin 5-HT6 receptor weak partial agonist, serotonin 5-HT7 receptor inverse agonist, and serotonin 5-HT1D receptor ligand.[13][14] It also showed weak affinity for other serotonin receptors, including for the serotonin 5-HT2A receptor (59.9% binding inhibition at 10 μM).[13] In rodents, pellotine dose-dependently produces hypolocomotion, inhibits REM sleep, and promotes sleep fragmentation.[13] The hypnotic effects of pellotine may be mediated by interactions with serotonin receptors.[13] Doses of 8 to 10 mg of isolated pellotine are known to cause convulsions in frogs.[15]

Chemistry

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Synthesis

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The chemical synthesis of pellotine has been described.[11][16]

Analogues

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Analogues of pellotine include anhalamine, anhalidine, anhalinine, anhalonidine, and gigantine, among others.[11][17][18][1][3][19]

Natural occurrence

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Pellotine has been isolated from numerous species of cactus, including Gymnocalycium, Lophophora, Turbinicarpus species, among others.[11] It is the major alkaloid in Lophophora diffusa (false peyote), where it makes up 86% to more than 90% of alkaloid content.[2][5][11] On the other hand, it is the second most common alkaloid found in Lophophora williamsii (peyote), constituting 17 to 18% of alkaloid content.[2][5][20][11][21] For comparison, other alkaloid contents in peyote are mescaline 30%, anhalonidine 14%, anhalamine 8%, hordenine 8%, and lophophorine 5%.[2][5][20][21] Pellotine is also found in large amounts Lophophora fricii (65% alkaloid content).[4][11]

History

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Native inhabitants of north-eastern Mexico around 810 to 1070 CE (according to carbon dating) are thought to have used a number of "mescal buttons" (cacti of the genus Lophophora) containing mescaline, pellotine, and other related alkaloids. While it is known that the cytisine-containing "mescal beans" were at least ornamental, it is unclear whether "mescal buttons" were ornamental or used for their psychoactive effects.[22]

Arthur Heffter isolated pellotine from a Lophophora, most likely Lophophora diffusa, and described it in the scientific literature in 1894.[3][23] It was the first alkaloid he isolated from Lophophora.[2] Through self-experiments, Heffter found that pellotine produced marked but short-lasting hypnotic effects.[3] In contrast to mescaline, which he discovered later, pellotine produced no hallucinogenic effects even at high doses.[3]

Subsequent to its discovery by Heffter, pellotine was studied as a hypnotic in several hundred patients in Europe and was manufactured and sold as a sleep aid by Boehringer und Soun (Boehringer and Sons) in Germany in the 1890s.[3][5][24] However, it was abandoned after the barbiturates were developed and introduced in the 1900s and 1910s.[3][5][24] This was related to these synthetic compounds being inexpensive to make, whereas pellotine required costly and tedious isolation from peyote that it made it impractical.[3][5] In addition, pellotine was said to be not the most reliable or consistent sleep aid, and its effects were quite short-lived.[3]

Society and culture

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Names

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Pellotine and peyotine are sometimes confused.[2]

See also

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References

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  1. 1 2 3 Cassels BK (2019). "Alkaloids of the Cactaceae — The Classics". Natural Product Communications. 14 (1). doi:10.1177/1934578X1901400123. ISSN 1934-578X.
  2. 1 2 3 4 5 6 7 8 Bruhn JG, Holmstedt B (1973). "Early peyote research an interdisciplinary study". Economic Botany. 28 (4): 353–390. doi:10.1007/BF02862854. ISSN 0013-0001. In 1931, Robles and Gbmez Robleda published a study of the pharmacological action of pellotine. [...] Pellotine constitutes more than 90% of the L. diffusa alkaloids. [...] According to Heffter (1898a), pellotine in a dose of 0.24 g does not cause hallucinations. Robles and Gbmez Robleda (1931), using doses up to 0.30 g, observed disorientation in their subjects, who also reported hallucinations.
  3. 1 2 3 4 5 6 7 8 9 10 11 Daniel M. Perrine (2001). "Visions of the Night Western Medicine Meets Peyote 1887-1899" (PDF). The Heffter Review of Psychedelic Research. 2: 6–52.
  4. 1 2 3 Chan CB, Poulie CB, Wismann SS, Soelberg J, Kristensen JL (August 2021). "The Alkaloids from Lophophora diffusa and Other "False Peyotes"". Journal of Natural Products. 84 (8): 2398–2407. doi:10.1021/acs.jnatprod.1c00381. PMID 34264089.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 Doesburg-van Kleffens M, Zimmermann-Klemd AM, Gründemann C (December 2023). "An Overview on the Hallucinogenic Peyote and Its Alkaloid Mescaline: The Importance of Context, Ceremony and Culture". Molecules. 28 (24). Basel, Switzerland: 7942. doi:10.3390/molecules28247942. PMC 10746114. PMID 38138432.
  6. ↑ Gabermann V (February 1978). "[Estimation of mescaline and pellotine in Lophophora coulter plants (Cactaceae) by means of the oscillographic polarography]". Biokhimiia. 43 (2). Moscow, Russia: 246–251. PMID 647075.
  7. 1 2 3 Jones P (2007). "The American Indian Church and its sacramental use of peyote: A review for professionals in the mental-health arena". Mental Health, Religion & Culture. 8 (4): 277–290. doi:10.1080/13674670412331304348. S2CID 144932041.
  8. 1 2 AIPSIN. "Пеллотин (Pellotine)". АИПСИН (in Russian). Retrieved 1 January 2026.
  9. 1 2 3 Shulgin AT (March 1973). "Mescaline: the chemistry and pharmacology of its analogs". Lloydia. 36 (1): 46–58. PMID 4576313. The pharmacological action of peyotline in human subjects is one of calming or sedation, rather than that of a hallucinogen. Jolly (14) has reported the production of an uneventful sleep in patients with a dosage of 50 mg. At levels of as much as 240 mg (total dosage) there are no indications of sensory distortions (5). There is a dizziness and a generalized tiredness that undergoes a gentle transition into sleep. This latter quantity of drug is greater than that which would be encountered in a single dosage unit of peyote. It is certainly possible that peyotline could contribute to the pharmacological picture associated with peyote as this sedative action is noted at levels that might well be encountered in the total cactus. At low levels in man (15-30 mg) there has been described a calming effect, without overt hypnosis (14).
  10. 1 2 Mangner TJ (1978). Potential Psychotomimetic Antagonists. N,n -diethyl-1-methyl-3-aryl-1, 2, 5, 6-tetrahydropyridine-5-carboxamides (Ph.D. thesis). University of Michigan. doi:10.7302/11268. Archived from the original on 30 March 2025. In addition to compounds strictly related to mescaline just described, L. williamsii also contains at least 23 variously substituted tetrahydroisoquinolines,95 of which four have been clinically tested. The two phenolic tetrahydroisoquinolines peyotline (63a) and anhalonidine (63b) were found to produce no sensory distortions, characteristic of the effects of mescaline, at doses of up to 250 mg.98 These compounds appear to induce a calming or sedative effect rather than a psychotomimetic one. Two methylenedioxy tetrahydroisoquinolines, lophophorine (64a) and anhalonine (64b), were also found to lack any psychotomimetic-type effects.98
  11. 1 2 3 4 5 6 7 Keeper Trout & friends (2013). Trout's Notes on The Cactus Alkaloids Nomenclature, Physical properties, Pharmacology & Occurrences (Sacred Cacti Fourth Edition, Part C: Cactus Chemistry: Section 1) (PDF). Mydriatic Productions/Better Days Publishing. A possible exception MAY be pellotine. Its primary action is as a sedative but in human trials using dosages as high as 300 mg some visual hallucinations were reported in ONE paper. This has neither been confirmed nor investigated further. Additionally, there have been several reports of hallucinogenic activity due to ingestion of L. diffusa which contains this as its main alkaloid. These stand at odds with all other evaluations of the pharmacological action of this alkaloid, as well as every other report on the ingestion of said cactus species. Most have dismissed the positive reports as using improperly identified specimens but we believe further study is called for. The only report of activity for peyotine was also the only report that evaluated dosages up to 300 mg. See under Pellotine. [...] Pellotine (Peyotline): [...] Heffter found a dose of 240 mg did not produce hallucinations [Heffter 1898a] [...] Robles & Gomez Robleda 1931 using doses of up to 300 mg observed disorientation and reported hallucinations were experienced by their subjects.
  12. ↑ Robles C, Gomez Robleda J (1931). "Trabajo inicial acerca de la accion fisiologica del clorhidrato de peyotina" [Preliminary study on the physiological action of peyotine hydrochloride]. Anales del Instituto de Biología, UNAM. 2 (1): 15–46. Las dosis medias (hasta 0.30 gr.) fueron las que empleamos con mayor frecuencia, ya que nos permitieron hacer las observaciones que a continuación presentanos. [...]
  13. 1 2 3 4 Poulie CB, Chan CB, Parka A, Lettorp M, Vos J, Raaschou A, et al. (October 2023). "In Vitro and In Vivo Evaluation of Pellotine: A Hypnotic Lophophora Alkaloid". ACS Pharmacology & Translational Science. 6 (10): 1492–1507. doi:10.1021/acsptsci.3c00142. PMC 10580395. PMID 37854625.
  14. ↑ Chan CB, Pottie E, Simon IA, Rossebø AG, Herth MM, Harpsøe K, et al. (February 2025). "Synthesis, Pharmacological Characterization, and Binding Mode Analysis of 8-Hydroxy-Tetrahydroisoquinolines as 5-HT7 Receptor Inverse Agonists". ACS Chemical Neuroscience. 16 (3): 439–451. doi:10.1021/acschemneuro.4c00667. PMID 39836645.
  15. ↑ Heffter A (1894). "Ueber Pellote". Archiv für Experimentelle Pathologie und Pharmakologie. 34 (1–2): 65–86. doi:10.1007/bf01864855. S2CID 28789116.
  16. ↑ Takido M, Khanna KL, Paul AG (February 1970). "New synthesis of rac. anhalonidine and rac. pellotine". Journal of Pharmaceutical Sciences. 59 (2): 271–273. doi:10.1002/jps.2600590232. PMID 5411355.
  17. ↑ Reti L (1954). "Chapter 26 Simple Isoquinoline Alkaloids". The Alkaloids: Chemistry and Physiology. Vol. 4. Elsevier. pp. 7–21. doi:10.1016/s1876-0813(08)60153-0. ISBN 978-0-12-469504-7. {{cite book}}: ISBN / Date incompatibility (help)
  18. ↑ Lundström J (1985). "The Occurrence of Simple Isoquinolines in Plants". The Chemistry and Biology of Isoquinoline Alkaloids. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 47–61. doi:10.1007/978-3-642-70128-3_4. ISBN 978-3-642-70130-6.
  19. ↑ Anderson EF (1996). Peyote: The Divine Cactus (2 ed.). University of Arizona Press. ISBN 978-0-8165-1654-4. Archived from the original on 22 September 2022.
  20. 1 2 Kapadia GJ, Fayez MB (March 1973). "The chemistry of peyote alkaloids". Lloydia. 36 (1): 9–35. PMID 4593882. Archived from the original on 27 June 2026.
  21. 1 2 Lundström J (June 1971). "Biosynthetic studies on mescaline and related cactus alkaloids". Acta Pharmaceutica Suecica. 8 (3): 275–302. PMID 5560272.
  22. ↑ El-Seedi HR, De Smet PA, Beck O, Possnert G, Bruhn JG (October 2005). "Prehistoric peyote use: alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas". Journal of Ethnopharmacology. 101 (1–3): 238–242. doi:10.1016/j.jep.2005.04.022. PMID 15990261.
  23. ↑ Heffter A (1894). "Ueber Pellote: Ein Beitrag zur pharmakologischen Kenntniss der Cacteen". Archiv für Experimentelle Pathologie und Pharmakologie (in German). 34 (1–2): 65–86. doi:10.1007/BF01864855. ISSN 0028-1298.
  24. 1 2 Dinis-Oliveira RJ, Pereira CL, da Silva DD (2019). "Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions". Curr Mol Pharmacol. 12 (3): 184–194. doi:10.2174/1874467211666181010154139. PMC 6864602. PMID 30318013. About a century ago, pellotine was marketed as a sedative/hypnotic by Boehringer & Sohn in Germany, but it was then discontinued after the advent of barbiturates. Worth to note that pellotine is the second most abundant alkaloid in Lophophora williamsii, but it is by far the most abundant alkaloid in the other Lophophora spp., accounting for 70- 90% of its total alkaloid content. In those species, mescaline is present only in trace concentrations, not necessarily high enough to produce pharmacological effects following ingestion of the cactus.
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