2,5-Dimethoxy-4-tert-butylamphetamine

2,5-Dimethoxy-4-tert-butylamphetamine (DOTB or DOtBu) is a non-hallucinogenic serotonin receptor modulator of the phenethylamine, amphetamine, and DOx families.^[1][2][3][4]

2,5-Dimethoxy-4-tert-butylamphetamine

Clinical data
Other names	2,5-Dimethoxy-4-tert-butylamphetamine; DOTB; DOtBu; 4-tert-Butyl-2,5-dimethoxyamphetamine
Routes of administration	Oral
Drug class	Serotonin receptor modulator; Serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor modulator
Identifiers
IUPAC name 1-(4-tert-butyl-2,5-dimethoxyphenyl)propan-2-amine
CAS Number	42456-77-9 Y
PubChem CID	12262514
ChemSpider	10440072
ChEMBL	ChEMBL8317
CompTox Dashboard (EPA)	DTXSID10874754
Chemical and physical data
Formula	C15H25NO2
Molar mass	251.370 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CC1=CC(=C(C=C1OC)C(C)(C)C)OC)N
InChI InChI=1S/C15H25NO2/c1-10(16)7-11-8-14(18-6)12(15(2,3)4)9-13(11)17-5/h8-10H,7,16H2,1-6H3 Key:RUAUPNFNQOGIFF-UHFFFAOYSA-N

Dosage and effects

According to Alexander Shulgin and colleagues, DOTB has been found to be inactive in humans at oral doses of up to 25 mg.^{[3][5][6][7][8]}

Pharmacology

Pharmacodynamics

DOTB binds with high affinity to the serotonin 5-HT₂ receptors, including to the serotonin 5-HT_2A and 5-HT_2C receptors and, to about a 10-fold lesser extent, to the serotonin 5-HT_2B receptor.^{[9][10][11][12]} It has been found to act as a partial agonist of the serotonin 5-HT_2A receptor, with an intrinsic efficacy of about 30% for phosphatidylinositol hydrolysis and about half of the efficacy of (R)-DOB.^[13][14] DOTB has also been assessed and found to act as a partial agonist of the serotonin 5-HT_2B receptor (E_maxTooltip maximal efficacy = 69%).^[10]

The drug appeared to be inactive in animals in the conditioned avoidance test in rodents.^[3][15] DOTB only partially substituted for DOM in rodent drug discrimination tests (up to 70% responding, followed by disruption at higher doses) and with much lower potency than other DOx drugs.^[16][17] In combination with DOM, DOTB produced some antagonism of the stimulus generalization of DOM, suggesting action as a lower-efficacy partial agonist of the serotonin 5-HT_2A receptor.^[12] Unlike DOM but similarly to DOAM, DOTB did not substitute for 5-MeO-DMT in rodent drug discrimination tests.^[5] It also did not affect locomotor activity in rodents, again in contrast to other DOx drugs, though there were non-significant increases in locomotion at the highest assessed doses.^[14] It did still produce hyperthermia in rabbits similarly to other DOx drugs, albeit with dramatically reduced potency.^[18][15][5]

Chemistry

DOTB is part of the series of straight-chain and branched-chain 4-alkylated DOx drugs that also includes DOM, DOET, DOPR, DOBU, DOAM, and DOHx, among others.^[4][9][5]

Some other notable analogues of DOTB include DOBU (n-butyl), DOIB (iso-butyl), and DOSB (sec-butyl).^{[1][2][7][8][6]}

DOIB, DOSB, and DOTB.^{[1][2][7][8][6]}

History

DOTB was first described in the scientific literature by 1974.^[18] Its psychoactive effects were first assessed and described by Alexander Shulgin in 1975.^[5][19]

See also

• 2,5-Dimethoxy-4-tert-butylphenethylamine (2C-tBu)