Anhalinine
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| Other names | O-Methylanhalamine; 6,7,8-Trimethoxy-THIQ; Anhalanine; Mescaline-CR; Mescaline-THIQ |
| Drug class | Serotonin 5-HT7 receptor inverse agonist |
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| Formula | C12H17NO3 |
| Molar mass | 223.272 g·mol−1 |
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| Melting point | 60 to 61 °C (140 to 142 °F) [1] |
| Boiling point | 144 to 145 °C (291 to 293 °F) (at 0.1 Torr)[1] |
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Anhalinine, also known as O-methylanhalamine or mescaline-CR, is a tetrahydroisoquinoline alkaloid found in Lophophora williamsii (peyote) and other cacti.[2][3] It is structurally related to mescaline and is a cyclized phenethylamine analogue of mescaline.[2] Anhalinine is also pharmacologically active, but is only a minor constituent of peyote and is unlikely to contribute to its effects.[4][2][5][6]
Use and effects
[edit]Alexander Shulgin tried anhalinine at small doses of 0.5 to 4.3 mg but experienced no effects.[7]
Pharmacology
[edit]Pharmacodynamics
[edit]Simple tetrahydroisoquinoline alkaloids of mescaline-containing cacti like anhalinine have received relatively little investigation.[2] Arthur Heffter found several of them to produce no effects similar to those of mescaline.[2] However, some of them have been found to produce convulsions in animals at high doses.[2] Anhalinine specifically has been described as having "stimulant" properties due to inhibiting cholinergic neurotransmission.[8][5][9][2]
Anhalinine has since been found to act as a low-potency inverse agonist of the serotonin 5-HT7 receptor, with an EC50 of 2,722 nM and an Emax of –85%.[10] This was much less potent in terms of this action than certain other tetrahydroisoquinolines like pellotine and anhalidine.[10] Serotonin 5-HT7 receptor inverse agonism might be involved in the sedative and hypnotic effects of certain peyote alkaloids like pellotine and anhalonidine.[11]
Chemistry
[edit]Synthesis
[edit]The chemical synthesis of anhalinine has been described.[12][13]
Analogues
[edit]Analogues of anhalinine include anhalamine, anhalidine, anhalonidine, gigantine, and pellotine, among others.[2][3][12] Derivatives of anhalinine include N-methylanhalinine, O-methylanhalonidine (1-methylanhalinine), and O-methylpellotine (1,N-dimethylanhalinine), norweberine, weberine, and pachycereine, among others.[12]
Cyclized tetrahydroisoquinoline analogues of other psychoactive phenethylamines, besides anhalinine (mescaline-CR), are also known, for instance AMPH-CR, METH-CR, PMMA-CR, DOM-CR, DOB-CR, MDA-CR, and MDMA-CR, among others.[14][15][16][17] In general, cyclization into tetrahydroisoquinolines results in abolition of their defining psychoactive effects and activities.[14][15][16][17] However, some tetrahydroisoquinolines show interactions with α2-adrenergic receptors and serotonin 5-HT1D, 5-HT6, and/or 5-HT7 receptors as well as effects related to these actions.[14][15][11][10]
Natural occurrence
[edit]Anhalinine has been isolated from numerous species of cactus, including Gymnocalycium, Lophophora, Pelecyphora, and Turbinicarpus species.[12][18][19] Depending on the species and methodology, the compound constitutes a total alkaloid fraction of 0.44 to 2.7% in Lophophora species, 2.88% in Pelecyphora pseudopectinata, and 0.15 to 39.57% in Turbinicarpus species.[12][18][19]
History
[edit]Anhalinine was first isolated from peyote by Ernst Späth in 1935.[20][12][6][13] Shulgin bioassayed it in 1963.[7]
See also
[edit]References
[edit]- 1 2 Taylor EP (1952). "236. Synthetic neuromuscular blocking agents. Part III. Miscellaneous quaternary ammonium salts". Journal of the Chemical Society (Resumed): 1309. doi:10.1039/jr9520001309.
- 1 2 3 4 5 6 7 8 Cassels BK (2019). "Alkaloids of the Cactaceae — The Classics". Natural Product Communications. 14 (1) 1934578X1901400123. doi:10.1177/1934578X1901400123. ISSN 1934-578X.
In contrast to mescaline and hordenine, the simple isoquinoline alkaloids of cacti have attracted little interest. The late 19th century efforts of Heffter and other authors, who generally observed convulsions in different animal species at high doses, were promptly reviewed by Affanasia Mogilewa (1903) who extended her studies to the isolated frog heart [56]. Some of Heffter's self-experiments revealed nothing of interest and, specifically, no effects remotely resembling those of mescaline. [...] A more recent exploration of mescaline and its 1,2,3,4-tetrahydroisoquinoline analog anhalinine at the neuromuscular junction of the frog and nicotinic receptors in rat brain cortex showed that both alkaloids inhibit neuromuscular transmission by blocking acetylcholine release. In the brain they failed to block [125I]α-bungarotoxin binding to nicotinic receptors [59], but this only reflects their low affinity for homomeric α7 and related receptors, and not for the predominant α4β2 subtype.
- 1 2 Lundström J (1985). "The Occurrence of Simple Isoquinolines in Plants". The Chemistry and Biology of Isoquinoline Alkaloids. Proceedings in Life Sciences. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 47–61. doi:10.1007/978-3-642-70128-3_4. ISBN 978-3-642-70130-6.
- ↑ Dinis-Oliveira RJ, Pereira CL, da Silva DD (2019). "Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions". Current Molecular Pharmacology. 12 (3): 184–194. doi:10.2174/1874467211666181010154139. PMC 6864602. PMID 30318013.
- 1 2 Ghansah E, Kopsombut P, Malleque MA, Brossi A (February 1993). "Effects of mescaline and some of its analogs on cholinergic neuromuscular transmission". Neuropharmacology. 32 (2): 169–174. doi:10.1016/0028-3908(93)90097-m. PMID 8383816.
- 1 2 Schultes RE (1937). "Peyote and Plants Used in the Peyote Ceremony". Botanical Museum Leaflets, Harvard University. 4 (8). Harvard University Herbaria: 129–152. doi:10.5962/p.236321. ISSN 0006-8098. JSTOR 41762641.
Anhalinine and Anhalidine have only recently been isolated and in amounts too minute to be of use in physiological tests.
- 1 2 Shulgin A (1963). Pharmacology Notebook 1. Subacute effects Anhalinine (PDF) (Report).
- ↑ 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.
- ↑ Vamvakopoulou IA, Narine KA, Campbell I, Dyck JR, Nutt DJ (January 2023). "Mescaline: The forgotten psychedelic". Neuropharmacology. 222 109294. doi:10.1016/j.neuropharm.2022.109294. PMID 36252614.
- 1 2 3 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. hdl:1854/LU-01JQ6WFR8R7G85440FRY2248HG. PMID 39836645.
- 1 2 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.
- 1 2 3 4 5 6 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.
- 1 2 Späth E, Becke F (6 March 1935). "Über ein neues Kakteen-Alkaloid, das Anhalinin, und zur Konstitution des Anhalonins (XIII. Mitteil. über Kakteen-Alkaloide)". Berichte der Deutschen Chemischen Gesellschaft (A and B Series). 68 (3): 501–505. doi:10.1002/cber.19350680324. ISSN 0365-9488.
- 1 2 3 Glennon RA, Young R (5 August 2011). "Role of Stereochemistry in Drug Discrimination Studies". Drug Discrimination. Wiley. pp. 129–161. doi:10.1002/9781118023150.ch4. ISBN 978-0-470-43352-2.
- 1 2 3 Glennon RA, Young R, Rangisetty JB (May 2002). "Further characterization of the stimulus properties of 5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline". Pharmacology, Biochemistry, and Behavior. 72 (1–2): 379–387. doi:10.1016/s0091-3057(01)00768-7. PMID 11900809.
- 1 2 Malmusi L, Dukat M, Young R, Teitler M, Darmani NA, Ahmad B, et al. (1996). "1, 2, 3, 4-Tetrahydroisoquinoline analogs of phenylalkylamine stimulants and hallucinogens". Medicinal Chemistry Research. 6 (6n): 400–441.
Conformationally constrained, 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs of central stimulant (e.g. amphetamine) and hallucinogenic (e.g. DOM) phenylalkylamines were prepared and evaluated to determine the contribution to activity of this conformational restriction. The amphetamine-related TIQs failed to produce locomotor stimulation in mice and did not produce amphetamine-appropriate responding in tests of stimulus generalization in (+)amphetamine-trained rats. Hallucinogen-related TIQs lacked appreciable affinity for 5-HT2A serotonin receptors and did not produce DOM-like effects in tests of stimulus generalization in DOM-trained rats. It is concluded that the phenylalkylamine conformation represented by the TIQs is not a major contributor to these actions.
- 1 2 Malmusi L, Dukat M, Young R, Teitler M, Darmani NA, Ahmad B, et al. (1996). "1,2,3,4-Tetrahydroisoquinoline and related analogs of the phenylalkylamine designer drug MDMA". Medicinal Chemistry Research. 6 (6): 412–426.
1,2,3,4-Tetrahydroisoquinoline (TIQ) analogs of 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) and its N-methyl derivative, MDMA, similar in structure to a TIQ metabolite of MDA, were prepared and examined (a) in tests of central stimulant activity in mice, (b) for their ability to bind at human 5-HT2A receptors, and (c) in tests of stimulus generalization in rats trained to discriminate MDMA from vehicle. In general, the TIQ analogs failed to display appreciable activity in any assay system. Conversely, certain 2-aminotetralin and 2-aminoindan analogs were active in the stimulus generalization studies. It is concluded that TIQ-like conformations do not account for the actions typically associated with MDA- and MDMA-related agents.
- 1 2 Chan CB, Poulie CB, Wismann SS, Soelberg J, Kristensen JL (August 2021). "The Alkaloids from Lophophora diffusa and Other "False Peyotes"". J Nat Prod. 84 (8): 2398–2407. doi:10.1021/acs.jnatprod.1c00381. PMID 34264089.
- 1 2 Štarha R, Chybidziurová A, Lacný Z (1999). "Alkaloids of the genus Turbinicarpus (Cactaceae)". Biochemical Systematics and Ecology. 27 (8): 839–841. doi:10.1016/S0305-1978(99)00019-8. Retrieved 30 June 2026.
- ↑ Kapadia GJ, Fayez MB (December 1970). "Peyote constituents: chemistry, biogenesis, and biological effects". Journal of Pharmaceutical Sciences. 59 (12): 1699–1727. Bibcode:1970JPhmS..59.1699K. doi:10.1002/jps.2600591202. PMID 5499699.
