Substituted 2-aminoindane


A substituted 2-aminoindane is a derivative of 2-aminoindane with one or more chemical substituents. They are cyclized phenethylamines and are structurally related to amphetamines like amphetamine and MDMA.
Many 2-aminoindanes are known to act as monoamine releasing agents and/or receptor modulators. They include psychoactive drugs, more specifically entactogens, stimulants, and psychedelics, and have been encountered as novel designer drugs. However, 2-aminoindanes are more selective for serotonin and/or norepinephrine release and are less effective at inducing dopamine release than their phenethylamine counterparts, are consequently less euphoric, and have not gained widespread popularity as recreational drugs. There is interest in entactogenic 2-aminoindanes for potential medical use, such as treatment of psychiatric disorders. One 2-aminoindane, MEAI, has been suggested as a possible alcohol alternative and substitute with better safety and less addictive potential.
Examples of 2-aminoindanes acting as monoamine releasing agents include 2-AI itself, NM-2-AI, MDAI, MMAI, MEAI, and 5-IAI, among others. DOM-AI is the 2-aminoindane analogue of the DOx psychedelic DOM and shows psychedelic-like effects in animals similarly but less potently. 2-Aminoindanes acting via other actions include aprindine, indantadol, and PNU-99,194, among others.

Use and effects

2-Aminoindanes acting as monoamine releasing agents variably produce entactogenic and/or stimulant effects. Serotonin-releasing 2-aminoindanes are described as less stimulating and much less euphoric than their phenethylamine counterparts. The next-day emotional hangover present with MDMA seems to be absent with these 2-aminoindanes, at least based on anecdotal user reports.

Pharmacology

Pharmacodynamics

2-Aminoindanes are known to act as monoamine releasing agents, including of serotonin, norepinephrine, and/or dopamine, among other actions such as α2-adrenergic receptor interactions. However, they are more selective for induction of serotonin and/or norepinephrine release than induction of dopamine release. This is thought to result in serotonin-releasing 2-aminoindanes having retained entactogenic effects but greatly reduced stimulating and euphoriant effects compared to their amphetamine counterparts.
Serotonin-releasing 2-aminoindanes show much less or no serotonergic neurotoxicity relative to MDMA. However, combination of serotonin-releasing 2-aminoindanes like MDAI or MMAI with amphetamine results in serotonergic neurotoxicity similar to that with MDMA. It is thought that robust simultaneous release of both serotonin and dopamine may be required for serotonergic neurotoxicity with MDMA-like drugs and that this is able to occur when serotonin-releasing aminoindanes are combined with an efficacious dopamine releaser like amphetamine.

History

The serotonin-releasing 2-aminoindanes like MDAI were developed by David E. Nichols and colleagues at Purdue University and were first described in 1990 followed by further publications throughout the rest of the 1990s.

List of substituted 2-aminoindanes

Monoamine releasing agents

Other agents

Related compounds

Indanorex is a 2-aminomethylindane, wherein the amino side chain has a methyl spacer. It was previously marketed under the brand name Dietor as a stimulant and appetite suppressant.
2-Aminotetralin and derivatives such as 6,7-methylenedioxy-2-aminotetralin and MDMAT are analogues of the 2-aminoindanes.
Jimscaline, 2CB-Ind, and AMMI are derivatives of 1-aminomethylindane, an indane- and amine-containing compound related to 1-aminoindane.
A number of notable derivatives of 1-aminoindane, a positional isomer of 2-AI, exist, such as rasagiline and ladostigil, among others.