DOM-AT

DOM-AT
Clinical data
Other names	DOM/AT; DOMAT; 5,8-Dimethoxy-6-methyl-2-aminotetralin
Identifiers
	IUPAC name 5,8-dimethoxy-6-methyl-1,2,3,4-tetrahydronaphthalen-2-amine;
CAS Number	53609-01-1;
PubChem CID	3016832;
ChemSpider	2284695;
ChEMBL	ChEMBL159379;
CompTox Dashboard (EPA)	DTXSID70968385 ;
Chemical and physical data
Formula	C13H19NO2
Molar mass	221.300 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC(=C2CC(CCC2=C1OC)N)OC;
	InChI InChI=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; Key:CEHNNXHZTWZRJP-UHFFFAOYSA-N;

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.^[1]^[2]^[3]^[4] It is specifically the cyclized 2-aminotetralin analogue of DOM.^[2]^[3]^[4]

The compound has been found to be a more potent agonist of peripheral serotonin receptors than DOM in vitro.^[4]^[2]^[5] This activity was blocked by the serotonin receptor antagonist cinanserin and by the non-hallucinogenic serotonin receptor modulator 2-bromo-LSD (BOL-148).^[2]^[5]^[3] However, DOM-AT was not tested for hallucinogen-type activity in animals or humans in these studies.^[4] 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).^[2]^[6]^[3] In cats, DOM-AT produced a rage reaction, while in rabbits, it produced behavioral excitation and hyperthermia.^[2]^[6] 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).^[7] Based on these findings, DOM-AT has been deemed inactive in terms of hallucinogen-like activity and unlikely to be psychedelic in humans.^[1]^[2]

DOM-AT was first described in the scientific literature by David E. Nichols in 1973.^[3]^[8]

Other cyclized analogues of DOM and related psychedelics include DOM-CR, DMCPA, TFMBOX, jimscaline, TCB-2, LPH-5, and ZC-B.^[1]^[4]^[2]

References

^ ^a ^b ^c Nichols 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. ISBN 978-3-662-55878-2. PMID 28401524. 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).
^ ^a ^b ^c ^d ^e ^f ^g ^h Nichols DE, Weintraub HJ, Pfister WR, Yim GK (1978). "The use of rigid analogues to probe hallucinogen receptors" (PDF). NIDA Research Monograph (22): 70–83. PMID 101889. Archived from the 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.
^ ^a ^b ^c ^d ^e Nichols 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. PMID 4809251. 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.
^ ^a ^b ^c ^d ^e Monte 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. Retrieved 15 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.
^ ^a ^b Cheng 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. PMID 4809263.
^ ^a ^b Nichols DE (August 1981). "Structure-activity relationships of phenethylamine hallucinogens". Journal of Pharmaceutical Sciences. 70 (8): 839–849. Bibcode:1981JPhmS..70..839N. doi:10.1002/jps.2600700802. PMID 7031221. 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).
^ 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. PMID 1967651.
^ Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085. 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.

External links

DOM-AT – Isomer Design

[Nichols_2018-1] Nichols 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. ISBN 978-3-662-55878-2. PMID 28401524. 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).

[Nichols_1978-2] ^ ^a ^b ^c ^d ^e ^f ^g ^h Nichols DE, Weintraub HJ, Pfister WR, Yim GK (1978). "The use of rigid analogues to probe hallucinogen receptors" (PDF). NIDA Research Monograph (22): 70–83. PMID 101889. Archived from the 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.

[Nichols_1974-3] Nichols 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. PMID 4809251. 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.

[Monte_1995-4] Monte 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. Retrieved 15 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.

[Cheng_1974-5] Cheng 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. PMID 4809263.

[Nichols_1981-6] Nichols DE (August 1981). "Structure-activity relationships of phenethylamine hallucinogens". Journal of Pharmaceutical Sciences. 70 (8): 839–849. Bibcode:1981JPhmS..70..839N. doi:10.1002/jps.2600700802. PMID 7031221. 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).

[Nichols_1990-7] 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. PMID 1967651.

[Nichols_1973-8] Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085. 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.

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DOM-AT

See also

References

External links

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