Substituted tetrahydroisoquinoline


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 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, and MDMTHIQ, have been developed and characterized. 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

StructureNameChemical Name Counterpart
Tetrahydroisoquinoline 1,2,3,4-Tetrahydroisoquinolineβ-Phenethylamine
Longimammosine2-Methyl-6-hydroxy-THIQmeta-Tyramine
Longimammidine2-Methyl-8-hydroxy-THIQmeta-Tyramine
Longimammatine6-Methoxy-THIQ3-Methoxyphenethylamine
Weberidine7-Methoxy-THIQ4-Methoxyphenethylamine
Norsalsolinol6,7-Dihydroxy-THIQDopamine
Longimammamine2-Methyl-4,8-dihydroxy-THIQmeta-Octopamine
Salsolinol1-Methyl-6,7-dihydroxy-THIQDopamine
Salsoline1-Methyl-6-hydroxy-7-methoxy-THIQ3-Hydroxy-4-methoxyphenethylamine
Isosalsoline1-Methyl-6-methoxy-7-hydroxy-THIQ3-Methoxytyramine
N-Methylisosalsoline1,2-Dimethyl-6-methoxy-7-hydroxy-THIQ3-Methoxytyramine
Arizonine1-Methyl-7-methoxy-8-hydroxy-THIQ3-Hydroxy-4-methoxyphenethylamine
Corypalline2-Methyl-6-methoxy-7-hydroxy-THIQ3-Methoxytyramine
Isocorypalline2-Methyl-6-hydroxy-7-methoxy-THIQ3-Hydroxy-4-methoxyphenethylamine
Uberine2-Methyl-5-methoxy-7-hydroxy-THIQ2-Methoxy-4-hydroxyphenethylamine
Hedycarine1--2-methyl-6-methoxy-7-hydroxy-THIQ3-Methoxytyramine
Lophocerine1--2-methyl-6-methoxy-7-hydroxy-THIQ3-Methoxytyramine
Heliamine6,7-Dimethoxy-THIQ3,4-Dimethoxyphenethylamine
Salsolidine1-Methyl-6,7-dimethoxy-THIQ3,4-Dimethoxyphenethylamine
N-Methylheliamine2-Methyl-6,7-dimethoxy-THIQ3,4-Dimethoxyphenethylamine
Lemaireocereine7,8-Dimethoxy-THIQ3,4-Dimethoxyphenethylamine
Carnegine1,2-Dimethyl-6,7-dimethoxy-THIQ3,4-Dimethoxyphenethylamine
Tepenine1,2-Dimethyl-7,8-dimethoxy-THIQ3,4-Dimethoxyphenethylamine
Calycotomine1--6,7-dimethoxy-THIQ3,4-Dimethoxyphenethylamine
Anhalamine6,7-Dimethoxy-8-hydroxy-THIQ3-Desmethylmescaline
Isoanhalamine6-Hydroxy-7,8-dimethoxy-THIQ3-Desmethylmescaline
Anhalidine2-Methyl-6,7-dimethoxy-8-hydroxy-THIQ3-Desmethylmescaline
Isoanhalidine2-Methyl-6-hydroxy-7,8-dimethoxy-THIQ3-Desmethylmescaline
Anhalonidine1-Methyl-6,7-dimethoxy-8-hydroxy-THIQ3-Desmethylmescaline
Isoanhalonidine1-Methyl-6-hydroxy-7,8-dimethoxy-THIQ3-Desmethylmescaline
Pellotine1,2-Dimethyl-6,7-dimethoxy-8-hydroxy-THIQ3-Desmethylmescaline
Peyotine1,2,2-Trimethyl-6,7-dimethoxy-8-hydroxy-THIQ3-Desmethylmescaline
Isopellotine1,2-Dimethyl-6-hydroxy-7,8-dimethoxy-THIQ3-Desmethylmescaline
Gigantine1,2-Dimethyl-5-hydroxy-6,7-dimethoxy-THIQ2-Hydroxy-3,4-dimethoxyphenethylamine
Deglucopterocereine1--2-methyl-5-hydroxy-6,7-dimethoxy-THIQ2-Hydroxy-3,4-dimethoxyphenethylamine
Anhalinine6,7,8-Trimethoxy-THIQMescaline
N-Methylanhalinine2-Methyl-6,7,8-trimethoxy-THIQMescaline
O-Methylanhalonidine1-Methyl-6,7,8-trimethoxy-THIQMescaline
O-Methylpellotine1,2-Dimethyl-6,7,8-trimethoxy-THIQMescaline
Nortehaunine5,6,7-Trimethoxy-THIQIsomescaline
Tehaunine2-Methyl-5,6,7-trimethoxy-THIQIsomescaline
Hydrocotarnine2-Methyl-6,7-methylenedioxy-8-methoxy-THIQLophophine
Anhalonine1-Methyl-6-methoxy-7,8-methylenedioxy-THIQLophophine
Anhalotine2,2-Dimethyl-6,7-dimethoxy-8-hydroxy-THIQ3-Desmethylmescaline
Lophophorine1,2-Dimethyl-6-methoxy-7,8-methylenedioxy-THIQLophophine
Lophotine1,2,2-Trimethyl-6-Methoxy-7,8-methylenedioxy-THIQLophophine
Peyophorine1-Methyl-2-ethyl-6-methoxy-7,8-methylenedioxy-THIQLophophine
Norweberine5,6,7,8-Tetramethoxy-THIQ2,3,4,5-Tetramethoxyphenethylamine
Weberine2-Methyl-5,6,7,8-tetramethoxy-THIQ2,3,4,5-Tetramethoxyphenethylamine
Pachycereine1-Methyl-5,6,7,8-tetramethoxy-THIQ2,3,4,5-Tetramethoxyphenethylamine
Tehaunine N-oxide2-Methyl-2-oxo-5,6,7-trimethoxy-THIQIsomescaline

Synthetic simple tetrahydroisoquinolines

StructureNameChemical Name Counterpart
Tetrahydroisoquinoline 1,2,3,4-TetrahydroisoquinolineAmphetamine
N-Methyl-THIQ 2-Methyl-THIQMethamphetamine
PMMA-CR2-Methyl-7-methoxy-THIQpara-Methoxymethamphetamine
DOM-CR5,8-Dimethoxy-7-methyl-THIQ2,5-Dimethoxy-4-methylamphetamine
DOB-CR5,8-Dimethoxy-7-bromo-THIQ2,5-Dimethoxy-4-bromoamphetamine
N-Methyl-DOM-CR2,7-Dimethyl-5,8-dimethoxy-THIQBeatrice
TDIQ 6,7-Methylenedioxy-THIQ3,4-Methylenedioxyamphetamine
Hydrohydrastinine 2-Methyl-6,7-methylenedioxy-THIQ3,4-Methylenedioxymethamphetamine
Hydrastinine1-Hydroxy-2-methyl-6,7-methylenedioxy-THIQ3,4-Methylenedioxymethamphetamine