^abcNichols DE (2018)."Chemistry and Structure-Activity Relationships of Psychedelics". In Halberstadt AL, Vollenweider FX, Nichols DE (eds.).Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43.doi:10.1007/7854_2017_475.ISBN978-3-662-55878-2.PMID28401524.Earlier studies had found that 2-aminotetralin and 2-aminoindan derivatives lacked activity, therefore indicating that the side chain probably could not reside in the plane of the aryl ring (Coutts and Malicky 1974; Nichols et al. 1974; Monte et al. 1998).
^abcdefghNichols DE, Weintraub HJ, Pfister WR, Yim GK (1978)."The use of rigid analogues to probe hallucinogen receptors"(PDF).NIDA Research Monograph (22):70–83.PMID101889. Archived fromthe original(PDF) on August 5, 2023.On the other hand, some interesting results have been obtained from studies using aminotetralin derivatives. Cheng et al. (1974), using a smooth muscle preparation, showed that aminotetralins are, in general, about 20-30 times more potent in eliciting contractions than are the correspondingly substituted phenylisopropylamines. A direct comparison between DOM 5 and the rigid analogues 6 (DOM-AT) and 7 (DOM-AI) showed 6 to be a more potent agonist at serotonin receptors than either DOM or the indan 7. The contractions induced by DOM or DOM-AT were completely blocked by cinanserin, a 5-HT antagonist. In the rat fundus, DOM-AT was much more potent than 7 and the contraction was blocked by BOL (Nichols et al. 1974). Behavioral tests in rats did not reveal a typical psychotomimetic-like profile for either 6 or 7. In cats, DOM-AT does elicit a sham rage reaction and in rabbits produces excitement and hyperthermia (unpublished results). Although nothing definite can be extrapolated from these studies to hallucinogenic effects in humans, it may be reasonable to conclude that there is a requirement for an extended planar side chain conformation in order to obtain effective binding at peripheral serotonin receptors and to elicit certain behavioral changes in animals.
^abcdeNichols DE, Barfknecht CF, Long JP, Standridge RT, Howell HG, Partyka RA, et al. (February 1974). "Potential psychotomimetics. 2. Rigid analogs of 2,5-dimethoxy-4-methylphenylisopropylamine (DOM, STP)".Journal of Medicinal Chemistry.17 (2):161–166.doi:10.1021/jm00248a004.PMID4809251.2-Amino-5,8-dimethoxy-6-methyl-l,2,3,4-tetrahydronaphthalene and 2-amino-4,7-dimethoxy-5-methylindan were prepared as rigid analogs of psychotomimetic phenylisopropylamines. Neither compound appeared to have psychotomimetic activity in rats. The effect of the aminotetralin derivative on 5-HT receptors in rat fundus strips and sheep umbilical arteries was also studied.
^abcdeMonte AP (August 1995).Structure-activity relationships of hallucinogens: Design, synthesis, and pharmacological evaluation of a series of conformationally restricted phenethylamines (Ph.D. thesis). Purdue University. Retrieved15 April 2025.Additionally, the side chain of DOM has been linked to the 6-position of the aromatic ring to produce the conformationally constrained aminotetralin (DOMAT) and aminoindan (DOMAI) analogs. In these studies, DOMAT was shown to be a more potent agonist at peripheral serotonin receptors than either DOM or DOMAI, however, these rigid analogs were not tested for in vivo hallucinogenic activity or for neuronal receptor binding affinities.
^abCheng HC, Long JP, Nichols DE, Barfknecht CF (January 1974). "Effects of psychotomimetics on vascular strips: studies of methoxylated amphetamines and optical isomers of 2,5-dimethoxy-4-methylamphetamine and 2,5-dimethoxy-4-bromoamphetamine".The Journal of Pharmacology and Experimental Therapeutics.188 (1):114–123.doi:10.1016/S0022-3565(25)29731-2.PMID4809263.
^Nichols DE, Brewster WK, Johnson MP, Oberlender R, Riggs RM (February 1990). "Nonneurotoxic tetralin and indan analogues of 3,4-(methylenedioxy)amphetamine (MDA)".Journal of Medicinal Chemistry.33 (2):703–710.doi:10.1021/jm00164a037.PMID1967651.
