A substituted 2-aminoindane is a derivative of 2-aminoindane (2-AI) 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 (5-MeO-2-AI), 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.

+ Compound Chemical name Dose Duration 2-AI 2-Aminoindane 10–20 mg (3–40 mg+) Unknown NM-2-AI N-Methyl-2-aminoindane 125 mg (20–300 mg+) Unknown MDAI 5,6-Methylenedioxy-2-aminoindane 100–200 mg (20–300 mg+) 2–5 hours MDMAI 5,6-Methylenedioxy-N-methyl-2-aminoindane Unknown Unknown MEAI (5-MeO-AI) 5-Methoxy-2-aminoindane 100–250 mg Unknown MMAI 5-Methoxy-6-methyl-2-aminoindane Unknown Unknown 5-IAI 5-Iodo-2-aminoindane 100–200 mg (20–200 mg) 2–4 hours Refs:

Pharmacology Pharmacodynamics + Compound Monoamine release (, nM) Ref 2-AI >10,000 86 439 MDAI 114 117 1,334 MDMAI MEAI 134 861 2,646 MMAI 31 3,101 >10,000 d-Amphetamine 698–1,765 6.6–7.2 5.8–24.8 MDA 160–162 47–108 106–190 MDMA 50–85 54–110 51–278 3-MA 58.0 103 MMA Notes: The smaller the value, the more strongly the compound produces the effect. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs:

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 2-Aminoindane (2-AI) 5,6-Benzofuranyl-2-aminoindane (BFAI) 5,6-Benzofuranyl-N-methyl-2-aminoindane (BFMAI) 5,6-Dihydroxy-2-aminoindane (DHAI) N-Ethyl-5-trifluoromethyl-2-aminoindane (ETAI) 1-(2-Indanyl)pyrrolidine (Pyr-AI, 2-PYI) 5-Iodo-2-aminoindane (5-IAI) 5-Iodo-N-methyl-2-aminoindane (5-IMAI) 5-Methoxy-2-aminoindane (MEAI, 5-MeO-2-AI) 5-Methoxy-6-methyl-2-aminoindane (MMAI) 5,6-Methylenedioxy-2-aminoindane (MDAI) 5,6-Methylenedioxy-N-methyl-2-aminoindane (MDMAI) N-Methyl-2-aminoindane (NM-2-AI) 5-Trifluoromethyl-2-aminoindane (TAI)

Other agents Aprindine (N-(diethylaminopropyl)-N-phenyl-2-aminoindane) – lidocaine-like antiarrhythmic agent DOM-AI (4,7-dimethoxy-5-methyl-2-aminoindane) – serotonergic psychedelic Indacaterol – β2-adrenergic receptor agonist Indantadol (N-glycinamidyl-2-aminoindane; CHF-3381) – anticonvulsant, neuroprotective agent, monoamine oxidase inhibitor, and NMDA receptor antagonist Moxaprindine (1-methoxyaprindine) [53076-26-9] – lidocaine-like antiarrhythmic agent PNU-99,194 (5,6-dimethoxy-N,N-dipropyl-2-aminoindane) – dopamine D3 receptor antagonist RD-211 (4-hydroxy-5-methyl-N,N-dipropyl-2-aminoindane) [103836-88-0] – dopamine D2 and serotonin 5-HT1A receptor agonist RDS-127 (4,7-dimethoxy-N,N-dipropyl-2-aminoindane) – dopamine D2 receptor agonist, other actions

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 (2-AT) and derivatives such as 6,7-methylenedioxy-2-aminotetralin (MDAT) 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.

See also Cyclized phenethylamine Substituted methylenedioxyphenethylamine (MDxx) Substituted benzofuran Substituted α-alkyltryptamine Borax combo

References