Simpleisoquinoline alkaloids of mescaline-containing cacti like anhalinine have received relatively little investigation.[2]Arthur Heffter found many of them to produce no effects similar to those of mescaline.[2] However, some of them have been found to produceconvulsions in animals at high doses.[2] Anhalinine specifically has been described as having "stimulant" properties due to inhibitingcholinergicneurotransmission.[7][5][8][2]Alexander Shulgin tried anhalinine at small doses of 0.5 to 4.3mg but experienced no effects.[9]
Anhalinine has been found to act as a low-potencyinverse agonist of theserotonin5-HT7 receptor, with anEC50Tooltip half-maximal effective concentration of 2,722nM and anEmaxTooltip half-maximal effective concentration of –85%.[10] This was much less potent in terms of this action than certain other tetrahydroisoquinolines likepellotine andanhalidine.[10] Serotonin 5-HT7 receptor inverse agonism might be involved in thesedative andhypnotic effects of certain peyote alkaloids like pellotine andanhalonidine.[11]
Cyclized tetrahydroisoquinoline analogues of otherpsychoactive phenethylamines, besides anhalinine (mescaline-CR), are also known, for instanceAMPH-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 withα2-adrenergic receptors andserotonin5-HT1D,5-HT6, and/or5-HT7 receptors as well as effects related to these actions.[14][15][11][10]
^abTaylor, E. P. (1952). "236. Synthetic neuromuscular blocking agents. Part III. Miscellaneous quaternary ammonium salts".Journal of the Chemical Society (Resumed): 1309.doi:10.1039/jr9520001309.
^abcdefgCassels, Bruce K. (2019)."Alkaloids of the Cactaceae — The Classics".Natural Product Communications.14 (1).doi:10.1177/1934578X1901400123.ISSN1934-578X.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.
^abGhansah 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.PMID8383816.
^abSchultes, Richard Evans (1937). "Peyote and Plants Used in the Peyote Ceremony".Botanical Museum Leaflets, Harvard University.4 (8). Harvard University Herbaria:129–152.ISSN0006-8098.JSTOR41762641.Anhalinine and Anhalidine have only recently been isolated and in amounts too minute to be of use in physiological tests.
^abcGlennon 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".Pharmacol Biochem Behav.72 (1–2):379–387.doi:10.1016/s0091-3057(01)00768-7.PMID11900809.
^abMalmusi, 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."
^abMalmusi, 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."
