A substituted tetrahydroisoquinoline is a tetrahydroisoquinoline with one or more chemical substituents. Many simple tetrahydroisoquinoline alkaloids related to mescaline are known and occur naturally in cactus species such as peyote (Lophophora williamsii) and Pachycereus pringlei among many others. Simple tetrahydroisoquinolines may be thought of as cyclized phenethylamines. As an example, anhalinine may be thought of as a cyclized analogue of mescaline. The simple tetrahydroisoquinolines are analogous in concept to the β-carbolines and harmala alkaloids, which can be considered cyclized analogues of tryptamines.
Some of the simple tetrahydroisoquinolines, for instance pellotine, are known to be pharmacologically active, although none are known to have hallucinogenic activity. Known activities of simple tetrahydroisoquinolines include sedative and hypnotic effects, monoamine oxidase inhibition, and convulsant effects, among various others. In the 2020s, various simple tetrahydroisoquinolines, like pellotine, were identified as serotonin 5-HT1D receptor ligands, serotonin 5-HT6 receptor partial agonists, and/or serotonin 5-HT7 receptor inverse agonists. These actions, such as the serotonin 5-HT6 and/or 5-HT7 receptor interactions, may be involved in the sedative and hypnotic effects of some of these compounds.
Synthetic tetrahydroisoquinoline analogues of phenethylamines, including AMPH-CR, METH-CR, PMMA-CR, DOM-CR, N-methyl-DOM-CR, DOB-CR, TDIQ (MDA-CR), and MDMTHIQ (MDMA-CR), have been developed and characterized.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 of stimulant, entactogen, and/or psychedelic phenethylamines into the corresponding tetrahydroisoquinolines results in abolition of the defining effects of these drugs as well as loss of their affinities for monoamine transporters and serotonin 5-HT2 receptors. However, some of the tetrahydroisoquinoline forms, such as TDIQ, show selective affinity for α2-adrenergic receptors and associated effects.
List of simple tetrahydroisoquinolines Simple tetrahydroisoquinoline alkaloids
Structure Name Chemical Name Counterpart Tetrahydroisoquinoline (THIQ) 1,2,3,4-Tetrahydroisoquinoline β-Phenethylamine Longimammosine 2-Methyl-6-hydroxy-THIQ meta-Tyramine Longimammidine 2-Methyl-8-hydroxy-THIQ meta-Tyramine Longimammatine 6-Methoxy-THIQ 3-Methoxyphenethylamine Weberidine 7-Methoxy-THIQ 4-Methoxyphenethylamine Norsalsolinol 6,7-Dihydroxy-THIQ Dopamine N-Methylnorsalsolinol 2-Methyl-6,7-dihydroxy-THIQ Dopamine Longimammamine 2-Methyl-4,8-dihydroxy-THIQ meta-Octopamine Salsolinol 1-Methyl-6,7-dihydroxy-THIQ Dopamine Salsoline 1-Methyl-6-hydroxy-7-methoxy-THIQ 3-Hydroxy-4-methoxyphenethylamine Isosalsoline 1-Methyl-6-methoxy-7-hydroxy-THIQ 3-Methoxytyramine N-Methylisosalsoline 1,2-Dimethyl-6-methoxy-7-hydroxy-THIQ 3-Methoxytyramine Arizonine 1-Methyl-7-methoxy-8-hydroxy-THIQ 3-Hydroxy-4-methoxyphenethylamine Corypalline 2-Methyl-6-methoxy-7-hydroxy-THIQ 3-Methoxytyramine Isocorypalline 2-Methyl-6-hydroxy-7-methoxy-THIQ 3-Hydroxy-4-methoxyphenethylamine Uberine 2-Methyl-5-methoxy-7-hydroxy-THIQ 2-Methoxy-4-hydroxyphenethylamine Hedycarine 1-(Hydroxymethyl)-2-methyl-6-methoxy-7-hydroxy-THIQ 3-Methoxytyramine Lophocerine 1-(2-Methylpropyl)-2-methyl-6-methoxy-7-hydroxy-THIQ 3-Methoxytyramine Heliamine 6,7-Dimethoxy-THIQ 3,4-Dimethoxyphenethylamine Salsolidine 1-Methyl-6,7-dimethoxy-THIQ 3,4-Dimethoxyphenethylamine N-Methylheliamine 2-Methyl-6,7-dimethoxy-THIQ 3,4-Dimethoxyphenethylamine Lemaireocereine 7,8-Dimethoxy-THIQ 3,4-Dimethoxyphenethylamine Carnegine 1,2-Dimethyl-6,7-dimethoxy-THIQ 3,4-Dimethoxyphenethylamine Tepenine 1,2-Dimethyl-7,8-dimethoxy-THIQ 3,4-Dimethoxyphenethylamine Calycotomine 1-(Hydroxymethyl)-6,7-dimethoxy-THIQ 3,4-Dimethoxyphenethylamine Anhalamine 6,7-Dimethoxy-8-hydroxy-THIQ 3-Desmethylmescaline Isoanhalamine 6-Hydroxy-7,8-dimethoxy-THIQ 3-Desmethylmescaline Anhalidine 2-Methyl-6,7-dimethoxy-8-hydroxy-THIQ 3-Desmethylmescaline Isoanhalidine 2-Methyl-6-hydroxy-7,8-dimethoxy-THIQ 3-Desmethylmescaline Anhalonidine 1-Methyl-6,7-dimethoxy-8-hydroxy-THIQ 3-Desmethylmescaline Isoanhalonidine 1-Methyl-6-hydroxy-7,8-dimethoxy-THIQ 3-Desmethylmescaline Pellotine 1,2-Dimethyl-6,7-dimethoxy-8-hydroxy-THIQ 3-Desmethylmescaline Peyotine 1,2,2-Trimethyl-6,7-dimethoxy-8-hydroxy-THIQ 3-Desmethylmescaline Isopellotine 1,2-Dimethyl-6-hydroxy-7,8-dimethoxy-THIQ 3-Desmethylmescaline Gigantine 1,2-Dimethyl-5-hydroxy-6,7-dimethoxy-THIQ 2-Hydroxy-3,4-dimethoxyphenethylamine Deglucopterocereine 1-(Hydroxymethyl)-2-methyl-5-hydroxy-6,7-dimethoxy-THIQ 2-Hydroxy-3,4-dimethoxyphenethylamine Anhalinine 6,7,8-Trimethoxy-THIQ Mescaline N-Methylanhalinine 2-Methyl-6,7,8-trimethoxy-THIQ Mescaline O-Methylanhalonidine 1-Methyl-6,7,8-trimethoxy-THIQ Mescaline O-Methylpellotine 1,2-Dimethyl-6,7,8-trimethoxy-THIQ Mescaline Nortehaunine 5,6,7-Trimethoxy-THIQ Isomescaline Tehaunine 2-Methyl-5,6,7-trimethoxy-THIQ Isomescaline Hydrocotarnine 2-Methyl-6,7-methylenedioxy-8-methoxy-THIQ Lophophine Anhalonine 1-Methyl-6-methoxy-7,8-methylenedioxy-THIQ Lophophine Anhalotine 2,2-Dimethyl-6,7-dimethoxy-8-hydroxy-THIQ 3-Desmethylmescaline Lophophorine 1,2-Dimethyl-6-methoxy-7,8-methylenedioxy-THIQ Lophophine Lophotine 1,2,2-Trimethyl-6-Methoxy-7,8-methylenedioxy-THIQ Lophophine Peyophorine 1-Methyl-2-ethyl-6-methoxy-7,8-methylenedioxy-THIQ Lophophine Norweberine 5,6,7,8-Tetramethoxy-THIQ 2,3,4,5-Tetramethoxyphenethylamine Weberine 2-Methyl-5,6,7,8-tetramethoxy-THIQ 2,3,4,5-Tetramethoxyphenethylamine Pachycereine 1-Methyl-5,6,7,8-tetramethoxy-THIQ 2,3,4,5-Tetramethoxyphenethylamine Tehaunine N-oxide 2-Methyl-2-oxo-5,6,7-trimethoxy-THIQ Isomescaline
Synthetic simple tetrahydroisoquinolines
Structure Name Chemical Name Counterpart Tetrahydroisoquinoline (THIQ; AMPH-CR) 1,2,3,4-Tetrahydroisoquinoline Amphetamine N-Methyl-THIQ (METH-CR) 2-Methyl-THIQ Methamphetamine PMMA-CR 2-Methyl-7-methoxy-THIQ para-Methoxymethamphetamine (PMMA) DOM-CR 5,8-Dimethoxy-7-methyl-THIQ 2,5-Dimethoxy-4-methylamphetamine (DOM) DOB-CR 5,8-Dimethoxy-7-bromo-THIQ 2,5-Dimethoxy-4-bromoamphetamine (DOB) N-Methyl-DOM-CR 2,7-Dimethyl-5,8-dimethoxy-THIQ Beatrice (N-methyl-DOM) TDIQ (MDTHIQ, MDA-CR) 6,7-Methylenedioxy-THIQ 3,4-Methylenedioxyamphetamine (MDA) Hydrohydrastinine (MDMTHIQ, MDMA-CR) 2-Methyl-6,7-methylenedioxy-THIQ 3,4-Methylenedioxymethamphetamine (MDMA) Hydrastinine 1-Hydroxy-2-methyl-6,7-methylenedioxy-THIQ 3,4-Methylenedioxymethamphetamine (MDMA) 3Me6,7MDTIQ 3-Methyl-6,7-methylenedioxy-THIQ 3,4-Methylenedioxyamphetamine (MDA) Esproquin 2-(3-Ethylsulfinylpropyl)-THIQ –
See also The Simple Plant Isoquinolines (2002) Substituted phenethylamine Substituted 3-benzazepine Substituted β-carboline and harmala alkaloid Iboga-type alkaloid and ibogalog A-69024 Metofoline
Notes
References
External links Structural Tables: Isoquinolines - Trout's Notes Isoquinolines: Structural Analogues of the Mysterious Third Family - Nikita Obidin