2,5-Dimethoxy-4-iodoamphetamine
Encyclopedia
2,5-dimethoxy-4-iodoamphetamine (DOI) is a psychedelic
drug
and a substituted amphetamine
of the phenethylamine
family. It is also a powerful anti-inflammatory that is effective at doses on the order of 100 micrograms in humans, far below its effective dose as a psychedelic. Despite being a substituted amphetamine
, it is not a stimulant
. 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 5-HT2A serotonin receptors
.
When ingested recreationally, DOI is active at a dosage of 1.5 - 3.0 mg (orally) and has a duration of 16 – 30 hours (approximately twice as long as LSD). 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. It is often 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. Unlike LSD, the psychedelic amphetamines (including DOI) can have harmful and potentially fatal physical effects in overdose. Although there have been no known deaths due to DOI ingestion, it is relatively new on the recreational scene so long-term effects are not known.
, 5-HT2B
, and 5-HT2C receptor
partial agonist
. Its psychedelic effects are mediated by its agonist
ic properties at the 5-HT2A receptor. Due to its selectivity, DOI is often used in scientific research when studying the 5-HT2 receptor subfamily.
The solubility of DOI hydrochloride in H2O is 10 mg/ml, and in ethanol 2 mg/ml.
DOI has also recently been shown to be an extremely potent inhibitor
of Tumor necrosis factor-alpha, an inflammatory mediator which is an important target for current research into degenerative conditions such as arthritis
and Alzheimer's disease
, where the disease process involves tissue damage through chronic inflammation. This could make DOI and other 5-HT2A agonists an entirely new area for development of novel treatments for these conditions.
. The radioactive iodine
-125 form of DOI was first developed in the lab of David E. Nichols
.
In January 2007, British Police reported that 3 young men had taken 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.
Given that it is structurally derived from phenethylamine through methoxy substitutions on the ring, it is a Class A drug in the UK.
An extremely large increase of the hallucinogenic drug has been seen in sales in Adelaide, Australia. It is commonly sold as LSD or just "trips".
Psychedelic
The term psychedelic is derived from the Greek words ψυχή and δηλοῦν , translating to "soul-manifesting". A psychedelic experience is characterized by the striking perception of aspects of one's mind previously unknown, or by the creative exuberance of the mind liberated from its ostensibly...
drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
and a substituted amphetamine
Substituted amphetamine
Substituted amphetamines are a chemical class of stimulants, entactogens, hallucinogens, and other drugs. They feature a phenethylamine core with a methyl group attached to the alpha carbon resulting in amphetamine, along with additional substitutions...
of the phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
family. It is also a powerful anti-inflammatory that is effective at doses on the order of 100 micrograms in humans, far below its effective dose as a psychedelic. Despite being a substituted amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, it is not a stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
. DOI has a stereocenter
Stereocenter
A stereocenter or stereogenic center is an atom, bearing groups such that an interchanging of any two groups leads to a stereoisomer.A chirality center is a stereocenter consisting of an atom holding a set of ligands in a spatial arrangement which is not superposable on its mirror image...
and R-(-)-DOI is the more active stereoisomer. In neuroscience research, [125I]-R-(-)-DOI is used as a radioligand
Radioligand
A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....
and indicator of the presence of 5-HT2A serotonin receptors
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
.
When ingested recreationally, DOI is active at a dosage of 1.5 - 3.0 mg (orally) and has a duration of 16 – 30 hours (approximately twice as long as LSD). 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. It is often 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. Unlike LSD, the psychedelic amphetamines (including DOI) can have harmful and potentially fatal physical effects in overdose. Although there have been no known deaths due to DOI ingestion, it is relatively new on the recreational scene so long-term effects are not known.
Pharmacology
DOI is a 5-HT2A5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
, 5-HT2B
5-HT2B receptor
5-hydroxytryptamine receptor 2B, also known as HTR2B, is a 5-HT2 receptor, but also denotes the human gene encoding it.-Function:...
, and 5-HT2C receptor
5-HT2C receptor
The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...
partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
. Its psychedelic effects are mediated by its agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
ic properties at the 5-HT2A receptor. Due to its selectivity, DOI is often used in scientific research when studying the 5-HT2 receptor subfamily.
The solubility of DOI hydrochloride in H2O is 10 mg/ml, and in ethanol 2 mg/ml.
DOI has also recently been shown to be an extremely potent inhibitor
TNF inhibitor
Tumor necrosis factor promotes the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, hidradenitis suppurativa and refractory asthma. These disorders are...
of Tumor necrosis factor-alpha, an inflammatory mediator which is an important target for current research into degenerative conditions such as arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
and Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, where the disease process involves tissue damage through chronic inflammation. This could make DOI and other 5-HT2A agonists an entirely new area for development of novel treatments for these conditions.
History
DOI was first synthesized by Alexander ShulginAlexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...
. The radioactive iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
-125 form of DOI was first developed in the lab of David E. Nichols
David E. Nichols
David E. Nichols is an American pharmacologist and medicinal chemist.Presently the Robert C. and Charlotte P. Anderson Distinguished Chair in Pharmacology at Purdue University, Nichols has worked in the field of psychoactive drugs since 1969...
.
In January 2007, British Police reported that 3 young men had taken ill, reportedly, after taking DOI at a rave in Biggleswade
Biggleswade
Biggleswade is a market town and civil parish located on the River Ivel in Bedfordshire, England. It is well served by transport routes, being close to the A1 road between London and the North, as well as having a railway station on the main rail link North from London .-Geography:Located about 40...
, near Milton Keynes
Milton Keynes
Milton Keynes , sometimes abbreviated MK, is a large town in Buckinghamshire, in the south east of England, about north-west of London. It is the administrative centre of the Borough of 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.
Given that it is structurally derived from phenethylamine through methoxy substitutions on the ring, it is a Class A drug in the UK.
An extremely large increase of the hallucinogenic drug has been seen in sales in Adelaide, Australia. It is commonly sold as LSD or just "trips".