Anhalinine

Anhalinine, also known as ''O''-methylanhalamine or mescaline-CR, is a tetrahydroisoquinoline alkaloid found in ''Lophophora williamsii'' (peyote) and other cacti. It is structurally related to mescaline and is a cyclized phenethylamine analogue of mescaline. Anhalinine is also pharmacologically active, but is only a minor constituent of peyote and is unlikely to contribute to its effects.

Simple isoquinoline alkaloids of mescaline-containing cacti like anhalinine have received relatively little investigation. Arthur Heffter found many of them to produce no effects similar to those of mescaline. However, some of them have been found to produce convulsions in animals at high doses. Anhalinine specifically has been described as having "stimulant" properties due to inhibiting cholinergic neurotransmission. Alexander Shulgin tried anhalinine at small doses of 0.5 to 4.3mg but experienced no effects.Alexander Shulgin. Pharmacology Notebook 1. Subacute effects Anhalinine. 1963. https://web.archive.org/web/20250416115643/https://www.erowid.org/library/books_online/shulgin_labbooks/shulgin_labbook1_searchable.pdf#page=81

Anhalinine has been found to act as a low-potency inverse agonist of the serotonin 5-HT₇ receptor, with an of 2,722nM and an of –85%. This was much less potent in terms of this action than certain other tetrahydroisoquinolines like pellotine and anhalidine. Serotonin 5-HT₇ receptor inverse agonism might be involved in the sedative and hypnotic effects of certain peyote alkaloids like pellotine and anhalonidine.

Anhalinine was first isolated from peyote by Ernst Späth in 1935. Shulgin bioassayed it in 1963.

Analogues

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.Malmusi, L., Dukat, M., Young, R., Teitler, M., Darmani, N. A., Ahmad, B., ... & Glennon, R. A. (1996). 1, 2, 3, 4-Tetrahydroisoquinoline analogs of phenylalkylamine stimulants and hallucinogens. ''Medicinal Chemistry Research'', ''6''(6), 400–411. https://scholar.google.com/scholar?cluster=16646102221398485716 "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."Malmusi, L., Dukat, M., Young, R., Teitler, M., Darmani, N. A., Ahmad, B., ... & Glennon, R. A. (1996). 1,2,3,4-Tetrahydroisoquinoline and related analogs of the phenylalkylamine designer drug MDMA. ''Medicinal Chemistry Research'', ''6''(6), 412–426. https://scholar.google.com/scholar?cluster=15073179555289853539 "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." In general, cyclization into tetrahydroisoquinolines results in abolition of their defining psychoactive effects and activities. However, some tetrahydroisoquinolines show interactions with α₂-adrenergic receptors and serotonin 5-HT_1D, 5-HT₆, and/or 5-HT₇ receptors as well as effects related to these actions.

See also

* Substituted tetrahydroisoquinoline
* Anhalamine
* Anhalidine
* Anhalonidine
* Gigantine
* Pellotine

References

{{Phenethylamines

5-HT7 antagonists
Lophophora
Norsalsolinol ethers
Pyrogallol ethers
Tetrahydroisoquinoline alkaloids