MDAI, also known as 5,6-methylenedioxy-2-aminoindane, is an entactogen drug of the 2-aminoindane group which is related to MDMA and produces similar subjective effects.
It acts as a selective serotonin and norepinephrine releasing agent (SNRA).
MDAI was developed in the 1990s by a team led by David E. Nichols at Purdue University.
Uses
Scientific research
MDAI and other similar drugs have been widely used in scientific research, as they are able to replicate many of the effects of MDMA, but without causing the serotonergic neurotoxicity associated with MDMA and certain related drugs. No tests have been performed on cardiovascular toxicity.
Recreational drug
MDAI has been advertised as a
designer drug. It started to be sold online from around 2007, but reached peak popularity between about 2010 to 2012, after bans on
mephedrone came into effect in various countries. Many internet-sourced products claimed to be MDAI have been shown to contain
mephedrone or other substituted cathinone derivatives, while generally containing no MDAI. The number of internet searches for MDAI has been considerably higher in the United Kingdom compared to Germany and the United States.
MDAI is only non-neurotoxic in isolation but may become neurotoxic when mixed with other drugs.
Three deaths were linked to MDAI use in the UK during 2011–2012, all involving symptoms consistent with serotonin syndrome. Two of these also involved other drugs while one death appeared to be from MDAI alone.
Pharmacology
Pharmacodynamics
MDAI acts as a selective and well-balanced serotonin and norepinephrine releasing agent (SNRA) with much less (~10-fold lower) effect on dopamine release.
In addition to inducing the release of the monoamine neurotransmitters, MDAI also inhibits their reuptake.
For comparison to MDAI, MDA and
MDMA are well-balanced releasing agents of serotonin, norepinephrine, and dopamine (SNDRAs).
Conversely, the profile of monoamine release with MDAI is very similar to that of (
R)-MDMA (
levo-MDMA), which like MDAI is also a well-balanced SNRA with about 10-fold reduced impact on dopamine release, though MDAI is several-fold more potent than (
R)-MDMA
in vitro.
In contrast to MDMA, MDAI shows no affinity for any of the serotonin receptors (Ki = all >10μM).
| + Activities of MDAI and related drugs |
|
|
| 439 |
| 1,334 |
| >10,000 |
| 2,646 |
| 5.8–24.8 |
| 8.5–24.5 |
| 190 |
| 51.2–278 |
| 3,700 |
| 622 |
| >100,000 |
Notes: The smaller the value, the more strongly the compound produces the effect. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: |
Effects
The family of drugs typified by
MDMA produce their effects through multiple mechanisms of action in the body, and consequently produce three distinct cues which animals can be trained to respond to: a stimulant cue typified by drugs such as
methamphetamine, a psychedelic cue typified by drugs such as
LSD and DOM, and an "entactogen-like" cue which is produced by drugs such as MDAI and
MBDB. These drugs cause drug-appropriate responses in animals trained to recognize the effects of MDMA, but do not produce responses in animals trained selectively to respond to stimulants or hallucinogens. Because these compounds selectively release serotonin in the brain but have little effect on dopamine or noradrenaline levels, they can produce empathogenic effects but without any stimulant action, instead being somewhat sedating.
[ PMID]
A 2024 study compared the effects of MDAI and MDMA in humans.
Neurotoxicity
MDAI shows substantially lower serotonergic neurotoxicity than
MDMA in animals and has been described as a "non-neurotoxic" analogue of MDMA.
However, MDAI still shows weak serotonergic neurotoxicity both alone and particularly in
combination drug with
amphetamine in animals.
As such, MDAI does not appear to be a fully non-neurotoxic alternative to MDMA.
Toxicity
Very high doses can be fatal in rats with a 50% fatality rate for those subcutaneously injected with 28 mg/kg of MDAI. This is a result of the way serotonin release interferes with thermoregulation.
Pharmacokinetics
The duration of MDAI in humans appears to be similar to that of MDMA at 2 to 5hours
or up to around 6hours.
Chemistry
The chemical structure of MDAI is indirectly derived from that of the illicit drug MDA, but the α-
methyl group of the
alkyl amino amphetamine side chain has been bound back to the
benzene nucleus to form an
indane ring system, which changes its pharmacological properties substantially.
Analogues
-
5,6-methylenedioxy-N-methyl-2-aminoindane
-
5-methoxy-2-aminoindane
-
5-methoxy-6-methyl-2-aminoindane
-
5-iodo-2-aminoindane
-
2-aminoindane
-
N-methyl-2-aminoindane
Synthesis
MDAI can be produced from 3-(3,4-methylenedioxyphenyl)propionic acid
which is converted to the acid chloride and then heated to produce 5,6-methylenedioxy-1-indanone. Treatment of the indanone with amyl nitrite in methanol with HCl afforded the hydroxyimino ketone. This is reduced to the 2-aminoindan following a modification of Nichols' earlier method from a paper discussing DOM analogues,
using a Pd/C catalyst in glacial
acetic acid with catalytic
sulfuric acid.
Society and culture
Legal Status
China
As of October 2015 MDAI is a controlled substance in
China.
Denmark
MDAI is illegal in
Denmark as of September 2015.
Finland
Scheduled in the "government decree on psychoactive substances banned from the consumer market".
[ finlex.fi]
Switzerland
As of December 2011 MDAI is a controlled substance in
Switzerland.
