DOM-AT

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| image = DOM-AT.svg

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| CAS_number = 53609-01-1

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| PubChem = 3016832

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| ChemSpiderID = 2284695

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| ChEMBL = 159379

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| synonyms = DOM/AT; DOMAT; 5,8-Dimethoxy-6-methyl-2-aminotetralin

| IUPAC_name = 5,8-dimethoxy-6-methyl-1,2,3,4-tetrahydronaphthalen-2-amine

| C=13 | H=19 | N=1 | O=2

| SMILES = CC1=CC(=C2CC(CCC2=C1OC)N)OC

| StdInChI = 1S/C13H19NO2/c1-8-6-12(15-2)11-7-9(14)4-5-10(11)13(8)16-3/h6,9H,4-5,7,14H2,1-3H3

| StdInChIKey = CEHNNXHZTWZRJP-UHFFFAOYSA-N

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DOM-AT, or DOMAT, also known as 5,8-dimethoxy-6-methyl-2-aminotetralin, is a cyclized phenethylamine and 2-aminotetralin related to the psychedelic amphetamine DOM.{{cite book | vauthors = Nichols DE | chapter = Chemistry and Structure-Activity Relationships of Psychedelics | veditors = Halberstadt AL, Vollenweider FX, Nichols DE | title = Behavioral Neurobiology of Psychedelic Drugs | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | chapter-url = https://bitnest.netfirms.com/external/10.1007/7854_2017_475 | quote = 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). }}{{cite journal | vauthors = Nichols DE, Weintraub HJ, Pfister WR, Yim GK | title = The use of rigid analogues to probe hallucinogen receptors | journal = NIDA Research Monograph | issue = 22 | pages = 70–83 | date = 1978 | pmid = 101889 | url = https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=81 | quote = 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. }}{{cite journal | vauthors = Nichols DE, Barfknecht CF, Long JP, Standridge RT, Howell HG, Partyka RA, Dyer DC | title = Potential psychotomimetics. 2. Rigid analogs of 2,5-dimethoxy-4-methylphenylisopropylamine (DOM, STP) | journal = Journal of Medicinal Chemistry | volume = 17 | issue = 2 | pages = 161–166 | date = February 1974 | pmid = 4809251 | doi = 10.1021/jm00248a004 | quote = 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. }}{{cite thesis | vauthors = Monte AP | title = Structure-activity relationships of hallucinogens: Design, synthesis, and pharmacological evaluation of a series of conformationally restricted phenethylamines | date = August 1995 | degree = Ph.D. | publisher = Purdue University | via = ProQuest | url = https://www.proquest.com/openview/68c29d003fe552ba4cf30ab8b617af29/1?cbl=18750&diss=y&pq-origsite=gscholar | access-date = 15 April 2025 | quote = 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. }} It is specifically the cyclized 2-aminotetralin analogue of DOM.

The compound has been found to be a more potent agonist of peripheral serotonin receptors than DOM in vitro. This activity was blocked by the serotonin receptor antagonist cinanserin and by the non-hallucinogenic serotonin receptor modulator 2-bromo-LSD (BOL-148).{{cite journal | vauthors = Cheng HC, Long JP, Nichols DE, Barfknecht CF | title = 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 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 188 | issue = 1 | pages = 114–123 | date = January 1974 | doi = 10.1016/S0022-3565(25)29731-2 | pmid = 4809263 }} However, DOM-AT was not tested for hallucinogen-type activity in animals or humans in these studies. Subsequently, DOM-AT did not appear to show a typical hallucinogen-like profile in behavioral tests in rats (e.g., the conditioned avoidance response test).{{cite journal | vauthors = Nichols DE | title = Structure-activity relationships of phenethylamine hallucinogens | journal = Journal of Pharmaceutical Sciences | volume = 70 | issue = 8 | pages = 839–849 | date = August 1981 | pmid = 7031221 | doi = 10.1002/jps.2600700802 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=f57e387fb5be33822c05b7a3b90888ee717aad21 | quote = Although none of the tetralins had clearcut hallucinogen-like action in any animal models, XXXVII produces hyperthermia in rabbits and evokes a rage response in cats (49). }} In cats, DOM-AT produced a rage reaction, while in rabbits, it produced behavioral excitation and hyperthermia. In later research, DOM-AT failed to substitute for LSD in rodent drug discrimination tests, whereas the related cyclized 2-aminoindan compound DOM-AI was effective, albeit with far lower potency than DOM (approximately 1/15th).{{cite journal | vauthors = Nichols DE, Brewster WK, Johnson MP, Oberlender R, Riggs RM | title = Nonneurotoxic tetralin and indan analogues of 3,4-(methylenedioxy)amphetamine (MDA) | journal = Journal of Medicinal Chemistry | volume = 33 | issue = 2 | pages = 703–710 | date = February 1990 | pmid = 1967651 | doi = 10.1021/jm00164a037 }} Based on these findings, DOM-AT has been deemed inactive in terms of hallucinogen-like activity and unlikely to be psychedelic in humans.

DOM-AT was first described in the scientific literature by David E. Nichols in 1973.{{cite thesis | vauthors = Nichols DE | title = Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid | pages = 23 | date = May 1973 | publisher = University of Iowa | oclc = 1194694085 | url = https://bitnest.netfirms.com/external/Theses/Nichols1973 | quote = Structure 44 was proposed for synthesis since it represents a rigid analog of DOM. It was felt that if the aminotetralin fragment in lysergic acid is the moiety responsible for the activity of LSD, then the fixed conformation of 44 might possess increased activity over that of DOM. }}

Other cyclized analogues of DOM and related psychedelics include DOM-CR, DMCPA, TFMBOX, jimscaline, TCB-2, LPH-5, and ZC-B.