Ortho-DOT, also known as 4,5-dimethoxy-2-methylthioamphetamine or as 2-thio-TMA-2, is a psychoactive drug of the phenethylamine and amphetamine families related to TMA-2. It is the analogue of TMA-2 in which the methoxy group at the 2 position has been replaced with a methylthio group. In addition, the drug is a positional isomer of Aleph (DOT; para-DOT).
In his book PiHKAL (Phenethylamines I Have Known and Loved) and other publications, Alexander Shulgin lists ortho-DOT's dose as greater than 25mg orally and its duration as unknown. The effects of ortho-DOT have been reported to include threshold effects, vague awareness, a feeling of an impending something, and gastrointestinal disturbance. No clear hallucinogenic effects were described. Shulgin concluded that ortho-DOT was inactive. Higher doses were not tested.
Ortho-DOT has been found to produce hyperthermia in rabbits, albeit with approximately 50-fold lower potency than DOM, though with somewhat greater potency than mescaline.
The chemical synthesis of ortho-DOT has been described. Analogues of ortho-DOT include TMA-2, Aleph (DOT; para-DOT; 4-thio-TMA-2), meta-DOT (5-thio-TMA-2), 2-TOM (2-thio-DOM), and 2-TOET (2-thio-DOET), among others.
Ortho-DOT was first described in the scientific literature by Shulgin and colleagues in 1977. Subsequently, it was described in greater detail by Shulgin in PiHKAL in 1991.