2,5-Dimethoxy-4-iodoamphetamine

DOI

Names
Preferred IUPAC name 1-(4-Iodo-2,5-dimethoxyphenyl)propan-2-amine
Identifiers
CAS Number	64584-34-5 82864-06-0 (R) N 99665-04-0 (S) N 42203-78-1 HCl
3D model (JSmol)	Interactive image Interactive image Interactive image
ChEMBL	ChEMBL6616 Y
ChemSpider	1192 Y
IUPHAR/BPS	147
PubChem CID	1229
UNII	Q2E57V2WS3 Y
CompTox Dashboard (EPA)	DTXSID7040520
InChI InChI=1S/C11H16INO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 Y Key: BGMZUEKZENQUJY-UHFFFAOYSA-N Y InChI=1/C11H16INO2/c1-7(13)4-8-5-11(15-3)9(12)6-10(8)14-2/h5-7H,4,13H2,1-3H3 Key: BGMZUEKZENQUJY-UHFFFAOYAA
SMILES IC(C=C1OC)=C(OC)C=C1CC(C)N IC(C=C1OC)=C(OC)C=C1C[C@@H](C)N IC(C=C1OC)=C(OC)C=C1C[C@H](C)N
Properties
Chemical formula	C11H16INO2
Molar mass	321.1558 g/mol
Melting point	201.5 °C (394.7 °F; 474.6 K) (hydrochloride)
Solubility in water	10 mg/mL[1]
Pharmacology
Legal status	BR: Class F2 (Prohibited psychotropics)[2] CA: Schedule I
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

2,5-Dimethoxy-4-iodoamphetamine (DOI) is a psychedelic drug of the amphetamine and 4-substituted-2,5-dimethoxyamphetamine (DOx) families.^[3][4]

DOI acts as a potent serotonin 5-HT₂ receptor agonist.^[3][4] DOI has a stereocenter and R-(−)-DOI is the more active stereoisomer. In neuroscience research, [¹²⁵I]-R-(−)-DOI is used as a radioligand and indicator of the presence of serotonin 5-HT_2A receptors.^[3]

DOI's effects have been compared to LSD, although there are differences that experienced users can distinguish. Besides the longer duration, the trip tends to be more energetic than an LSD trip, with more body load and a different subjective visual experience. The after effects include residual stimulation and difficulty sleeping, which, depending on the dose, may persist for days.^[5] While rare, it is sometimes sold as a substitute for LSD, or even sold falsely as LSD, which may be dangerous because DOI does not have the same established safety profile as LSD.^[6]

DOI was first synthesized in 1973, by Coutts and Malicky.^[3]

Research^[7] suggests that administration of (R)-DOI blocks pulmonary inflammation, mucus hyper-production, airway hyper-responsiveness and turns off key genes in in-lung immune response. These effects block the development of allergic asthma in a mouse model.

Several 5-HT_2A agonist hallucinogens including (R)-2,5-dimethoxy-4-iodoamphetamine DOI, TCB-2, LSD and LA-SS-Az have unexpectedly also been found to act as potent inhibitors of TNF, with DOI being the most active, showing TNF inhibition in the picomolar range, an order of magnitude more potent than its action as a hallucinogen.^[8][9][10]

DOI is a serotonin 5-HT_2A, 5-HT_2B and 5-HT_2C receptor agonist.^[4]

DOI has been shown to be an extremely potent inhibitor of tumour necrosis factor-alpha inflammation at picomolar concentrations in cell studies. TNF-alpha is an important target for research into degenerative conditions such as rheumatoid arthritis and Alzheimer's disease, where the disease process involves tissue damage through chronic inflammation. This could make DOI and other 5-HT_2A agonists an entirely new area for development of novel treatments for these conditions.^[12]

DOI has also been shown to induce rapid growth and reorganization of dendritic spines and synaptic connections with other neurons, processes known to underlie neuroplasticity.^[13]

The drug is not a monoamine releasing agent of serotonin or dopamine.^[14]

DOI is an agonist of the rat trace amine-associated receptor 1 (TAAR1).^[15]

DOI was first synthesized by Alexander Shulgin.^[5] The radioactive iodine-125 form of DOI for PET imaging was first developed in the lab of David E. Nichols.

In January 2007, British police reported that three young men had fallen ill, reportedly, after taking DOI at a rave in Biggleswade, near Milton Keynes, and warned others who had taken it to seek medical attention. This would appear to be the first indication that DOI has found more widespread use as a recreational drug in the UK.^[16]

South Australian man Cody Edwards who brutally murdered Synamin Bell controversially plead guilty to the lesser sentence of manslaughter after attesting that the drug DOI had induced paranoia, and that he had subsequently acted in ‘self-defence’ when he had beaten the mother-of-three to death with a dumbbell, resulting in over fifty wounds.^[17]

The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) of Australia does not list DOI as a prohibited substance.^[18]

Listed as a Schedule 1^[19] as it is an analogue of amphetamine.^[20] The CDSA was updated as a result of the Safe Streets and Communities Act, changing amphetamines from Schedule 3 to Schedule 1.^[21]

Illegal since 8 April 2007.^[22]

DOI is classified as a psychoactive substance banned from the consumer market in Finland.^[23]

Sveriges riksdag added DOI to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of August 30, 2007, published by Medical Products Agency in their regulation LVFS 2007:10 listed as DOI, 4-jod-2,5-dimetoxi-amfetamin.^[24]

As of 2023, DOI is not scheduled in the United States,^[25] but it is likely that DOI would be considered an analog (of DOB), in which case, sales or possession could be prosecuted under the Federal Analogue Act. In December 2023, the US Drug Enforcement Administration issued a notice of proposed rulemaking that would classify both 2,5-dimethoxy-4-iodoamphetamine and 2,5-dimethoxy-4-chloroamphetamine as schedule I controlled substances.^[26]

DOI is regularly used in animal and in vitro research.^[27] Scheduling DOI could cause problems for medical researchers.^[26]

DOI is a Schedule I controlled substance in the state of Florida.^[28]

• 2,5-Dimethoxy-4-Substituted Amphetamines
  • DOF
  • DOB
  • DOC

• Erowid about DOI
• The Lycaeum about DOI
• PiHKAL entry
• DOI Entry in PiHKAL • info