Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development
- Pharmaseed Ltd, Ness Ziona (Israel)
- Kimron Veterinary Institute, Department of Pathology, Bet Dagan (Israel)
- BSC BV Company, Veemarkt 61, Amsterdam (Netherlands)
- Imperial College London, Neuropsychopharmacology Unit, London (United Kingdom)
5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound of the aminoindane class, which in recent years has been recreationally used by many people, who reported of a mild euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. In the light of these observations it was decided to progress MEAI through a preliminary drug development route and evaluate the acute and subacute toxicity of MEAI administrated orally to Sprague Dawley rats, as well as to determine potential in-vitro cytotoxic and mutagenic effects using state-of-the-art protocols. Furthermore, the interaction of MEAI at the highest non-toxic concentration (100 mg/L) with ethanol at cytotoxic levels of 6% and 7.5% was explored, in order to identify possible additive or synergistic effects. MEAI showed a good safety profile in rats at 10 and 30 mg/kg body weight, corresponding to the human doses of 1.6 mg/kg and 4.8 mg/kg body weight, respectively. Cytotoxic effect was demonstrated using concentrations of 500 and 1000 mg/L with calculated IC{sub 50} value of 368.2 mg/L for rat brain striatum primary neurons and 403.1 mg/L for human primary healthy hepatocytes. The combination of 6% or 7.5% ethanol with 100 mg/L MEAI revealed no statistically significant increase of cytotoxic effect. Further studies, especially long term chronic and addictive behavior studies, are required in-order to assess MEAI safety profile. - Highlights: • Single oral administration of MEAI (10 mg/kg) to rats was well tolerated. • Five-day oral administration of MEAI (30 mg/kg) to rats was well tolerated. • Low cytotoxicity was observed in the in vitro cytotoxicity assays. • Ethanol-MEAI mixtures induced no synergistic/additive neurotoxicity.
- OSTI ID:
- 22690942
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 319; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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