OBJECTIVES: Aminoindanes ("bath salts," a class of novel psychoactive substances, NPSs) increased rapidly in popularity on the recreational drug market, particularly after mephedrone and other synthetic cathinones were banned in the UK in 2010. Novel aminoindanes continue to emerge, but relatively little is known about their effects and risks. Their history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity are reviewed in this paper. METHODS: Scientific literature was searched on ISI Web of Knowledge: Web of Science (WoS) during June and July 2017, using English language terms: aminoindanes such as 5,6-methylenedioxy-2-aminoindane (MDAI), 5-iodo-2-aminoindane (5-IAI), 2-aminoindane (2-AI), 5,6-methylenedioxy-N-methyl-2-aminoindane (MDMAI), and 5-methoxy-6-methyl-2-aminoindane (MMAI). WoS was selected as it searches several databases simultaneously and has quality criteria for inclusion. For typical use and effects, Erowid, PsychonautWiki, Bluelight, and Drugs-Forum were searched; for legal status and epidemiology, the European Information System and Database on New Drugs (EDND) was used. RESULTS: Aminoindanes were first synthesized for medical use, e.g., as anti-Parkinsonian drugs and later as a potential compound facilitating psychotherapy; however, they are now widely substituted for ecstasy. Their mechanisms of action (primarily via serotonin) mean that they may pose a significant risk of serotonin syndrome at high doses or when combined with other drugs. Fatally toxic effects have been observed both in the laboratory in animal studies and in clinic, where deaths related with aminoindanes have been reported. CONCLUSION: Greater knowledge about aminoindanes is urgently required to decrease risks of fatal intoxication, and appropriate legislation is needed to protect public health without impeding research.

3rd Medical Faculty Charles University Prague Czechia

National Institute of Mental Health Klecany Czechia

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EMCDDA. European Drug Report 2017: Trends and Developments (2017). Luxembourg: Publications Office of the European Union.

Brunt TM, Poortman A, Niesink RJM, van den Brink W. Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol (2011) 25(11):1543–7.10.1177/0269881110378370 PubMed DOI

Winstock A, Mitcheson L, Ramsey J, Davies S, Puchnarewicz M, Marsden J. Mephedrone: use, subjective effects and health risks. Addiction (2011) 106(11):1991–6.10.1111/j.1360-0443.2011.03502.x PubMed DOI

EDND. European Database on New Drugs (2017). Available from: https://ednd.emcdda.europa.eu

Leach B. New Drug to Replace Mephedrone as ‘Legal High’. The Telegraph; (2010). Available from: http://www.telegraph.co.uk/news/uknews/law-and-order/7602664/New-drug-to-replace-mephedrone-as-legal-high.html

Corkery JM, Elliott S, Schifano F, Corazza O, Ghodse AH. MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; “sparkle”; “mindy”) toxicity: a brief overview and update. Hum Psychopharmacol Clin Exp (2013) 28(4):345–55.10.1002/hup.2298 PubMed DOI

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol (2009) 62(10):1006–12.10.1016/j.jclinepi.2009.06.005 PubMed DOI

Fuller RW, Baker JC, Molloy BB. Biological disposition of rigid analogs of amphetamine. J Pharm Sci (1977) 66(2):271–2.10.1002/jps.2600660235 PubMed DOI

Nichols DE, Brewster WK, Johnson MP, Oberlender R, Riggs RM. Nonneurotoxic tetralin and indan analogs of 3,4-(methylenedioxy)amphetamine (MDA). J Med Chem (1990) 33(2):703–10.10.1021/jm00164a037 PubMed DOI

Oberlender R, Nichols DE. (+)-N-methyl-1-(1,3-benzodioxol-5-Yl)-2-butanamine as a discriminative stimulus in studies of 3,4-methylenedioxy-methamphetamine-like behavioral activity. J Pharmacol Exp Ther (1990) 255(3):1098–106. PubMed

Johnson MP, Frescas SP, Oberlender R, Nichols DE. Synthesis and pharmacological examination of 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan—similarities to 3,4-(methylenedioxy)methamphetamine (MDMA). J Med Chem (1991) 34(5):1662–8.10.1021/jm00109a020 PubMed DOI

Nichols DE, Johnson MP, Oberlender R. 5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine. Pharmacol Biochem Behav (1991) 38(1):135–9.10.1016/0091-3057(91)90601-W PubMed DOI

Maronalewicka D, Nichols DE. Behavioral-effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan. Eur J Pharmacol (1994) 258(1–2):1–13.10.1016/0014-2999(94)90051-5 PubMed DOI

Smith JP, Sutcliffe OB, Banks CE. An overview of recent developments in the analytical detection of new psychoactive substances (NPSs). Analyst (2015) 140(15):4932–48.10.1039/c5an00797f PubMed DOI

Shelton RS. Secondary Beta Phenyl Propyl Amines and Pharmaceutical Compositions Thereof. U.S. Patent No 2,298,630. Washington, DC: U.S. Patent and Trademark Office; (1942).

Woodruff EH. Amino Compound. U.S. Patent No 2,293,874. Washington, DC: U.S. Patent and Trademark Office; (1942).

Levin N, Graham BE, Kolloff HG. Physiologically active indanamines1. J Org Chem (1944) 09(4):380–91.10.1021/jo01186a010 DOI

Witkin LB, Heubner CF, Galdi F, O’Keefe E, Spitaletta P, Plummer AJ. Pharmacology of 2-amino-indane hydrochloride (Su-8629): a potent non-narcotic analgesic. J Pharmacol Exp Ther (1961) 133(3):400–8. PubMed

Solomons E, Sam J. 2-Aminoindans of pharmacological interest. J Med Chem (1973) 16(12):1330–3.10.1021/jm00270a004 PubMed DOI

Kier LB. The prediction of molecular conformation as a biologically significant property. Pure Appl Chem (1973) 35(4):509.10.1351/pac197335040509 DOI

Martin YC, Jarboe CH, Krause RA, Lynn KR, Dunnigan D, Holland JB. Potential anti-Parkinson drugs designed by receptor mapping. J Med Chem (1973) 16(2):147–50.10.1021/jm00260a014 PubMed DOI

Martin YC, Holland JB, Jarboe CH, Plotnikoff N. Discriminant analysis of the relation between physical properties and the inhibition of monoamine oxidase by aminotetralins and aminoindans. J Med Chem (1974) 17(4):409–13.10.1021/jm00250a008 PubMed DOI

Kalir A, Sabbagh A, Youdim MBH. Selective acetylenic suicide and reversible inhibitors of monoamine-oxidase type-A and type-B. Br J Pharmacol (1981) 73(1):55–64.10.1111/j.1476-5381.1981.tb16771.x PubMed DOI PMC

Youdim MBH, Gross A, Finberg JPM. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol (2001) 132(2):500–6.10.1038/sj.bjp.0703826 PubMed DOI PMC

Knudsen Gerber DS. Selegiline and rasagiline: twins or distant cousins? Consult Pharm (2011) 26(1):48–51.10.4140/TCP.n.2011.48 PubMed DOI

Nichols DE, Oberlender R, Burris K, Hoffman AJ, Johnson MP. Studies of dioxole ring substituted 3,4-methylenedioxyamphetamine (MDA) analogs. Pharmacol Biochem Behav (1989) 34(3):571–6.10.1016/0091-3057(89)90560-1 PubMed DOI

Nichols DE, Oberlender R. Structure-activity-relationships of mdma and related-compounds—a new class of psychoactive-drugs. Ann N Y Acad Sci (1990) 600:613–25.10.1111/j.1749-6632.1990.tb16914.x PubMed DOI

Johnson MP, Conarty PF, Nichols DE. [H-3] monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and para-chloroamphetamine analogs. Eur J Pharmacol (1991) 200(1):9–16.10.1016/0014-2999(91)90659-E PubMed DOI

Johnson MP, Huang X, Nichols DE. Serotonin neurotoxicity in rats after combined treatment with a dopaminergic agent followed by a nonneurotoxic 3,4-methylenedioxymethamphetamine (MDMA) analog. Pharmacol Biochem Behav (1991) 40(4):915–22.10.1016/0091-3057(91)90106-C PubMed DOI

Oberlender R, Nichols DE. Structural variation and (+)-amphetamine-like discriminative stimulus properties. Pharmacol Biochem Behav (1991) 38(3):581–6.10.1016/0091-3057(91)90017-V PubMed DOI

Monte AP, Maronalewicka D, Cozzi NV, Nichols DE. Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogs of 3,4-(methylenedioxy)amphetamine. J Med Chem (1993) 36(23):3700–6.10.1021/jm00075a027 PubMed DOI

Nichols DE, Hoffman AJ, Oberlender RA, Jacob P, Shulgin AT. Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class. J Med Chem (1986) 29(10):2009–15.10.1021/jm00160a035 PubMed DOI

Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME. Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives. Biochem Pharmacol (2014) 88(2):237–44.10.1016/j.bcp.2014.01.024 PubMed DOI

Palenicek T, Lhotkova E, Zidkova M, Balikova M, Kuchar M, Himl M, et al. Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): pharmacokinetics, behaviour, thermoregulation and LD50 in rats. Prog Neuropsychopharmacol Biol Psychiatry (2016) 69:49–59.10.1016/j.pnpbp.2016.04.004 PubMed DOI

Fitzgerald RL, Blanke RV, Poklis A. Stereoselective pharmacokinetics of 3,4-methylenedioxymethamphetamine in the rat. Chirality (1990) 2(4):241–8.10.1002/chir.530020409 PubMed DOI

Palenicek T, Balikova M, Rohanova M, Novak T, Horacek J, Fujakova M, et al. Behavioral, hyperthermic and pharmacokinetic profile of para-methoxymethamphetamine (PMMA) in rats. Pharmacol Biochem Behav (2011) 98(1):130–9.10.1016/j.pbb.2010.12.011 PubMed DOI

Palenicek T, Fujakova M, Brunovsky M, Horacek J, Gorman I, Balikova M, et al. Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats. Psychopharmacology (2013) 225(1):75–93.10.1007/s00213-012-2797-7 PubMed DOI

Palenicek T, Hlinak Z, Bubenikova-Valesova V, Novak T, Horacek J. Sex differences in the effects of N,N-diethyllysergamide (LSD) on behavioural activity and prepulse inhibition. Prog Neuropsychopharmacol Biol Psychiatry (2010) 34(4):588–96.10.1016/j.pnpbp.2010.02.008 PubMed DOI

Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (2001) 156(2–3):117–54.10.1007/s002130100811 PubMed DOI

Gatch MB, Dolan SB, Forster MJ. Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents. Behav Pharmacol (2016) 27(6):497–505.10.1097/Fbp.0000000000000237 PubMed DOI PMC

Coppola M. Is the 5-iodo-2-aminoindan (5-IAI) the new MDMA? J Addict Res Ther (2012) 03(04)1–3.10.4172/2155-6105.1000134 DOI

Coppola M, Mondola R. 5-Iodo-2-aminoindan (5-IAI): chemistry, pharmacology, and toxicology of a research chemical producing MDMA-like effects. Toxicol Lett (2013) 218(1):24–9.10.1016/j.toxlet.2013.01.008 PubMed DOI

PsychonautWiki. MDAI/Summary (2016). Available from: https://psychonautwiki.org/wiki/MDAI/Summary

PsychonautWiki. 2-Aminoindane (2016). Available from: https://psychonautwiki.org/wiki/2-Aminoindane

Drugs-Forum. 5-IAI (5-Iodo-2-Aminoindane) Trip Reports (2016). Available from: https://drugs-forum.com/forum/showthread.php?t=126985

Tormey WP, Moore T. Poisonings and clinical toxicology: a template for Ireland. Ir J Med Sci (2013) 182(1):17–23.10.1007/s11845-012-0828-3 PubMed DOI

Gallagher CT, Assi S, Stair JL, Fergus S, Corazza O, Corkery JM, et al. 5,6-methylenedioxy-2-aminoindane: from laboratory curiosity to ‘legal high’. Hum Psychopharmacol Clin Exp (2012) 27(2):106–12.10.1002/hup.1255 PubMed DOI

Staeheli SN, Boxler MI, Oestreich A, Marti M, Gascho D, Bolliger SA, et al. Postmortem distribution and redistribution of MDAI and 2-MAPB in blood and alternative matrices. Forensic Sci Int (2017) 279:83–7.10.1016/j.forsciint.2017.08.007 PubMed DOI

Elliott S, Evans J. A 3-year review of new psychoactive substances in casework. Forensic Sci Int (2014) 243:55–60.10.1016/j.forsciint.2014.04.017 PubMed DOI