Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development

Toxicol Appl Pharmacol. 2017 Mar 15:319:59-68. doi: 10.1016/j.taap.2017.01.018. Epub 2017 Feb 4.

Abstract

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 (100mg/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 30mg/kg body weight, corresponding to the human doses of 1.6mg/kg and 4.8mg/kg body weight, respectively. Cytotoxic effect was demonstrated using concentrations of 500 and 1000mg/L with calculated IC50 value of 368.2mg/L for rat brain striatum primary neurons and 403.1mg/L for human primary healthy hepatocytes. The combination of 6% or 7.5% ethanol with 100mg/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.

Keywords: 5-Methoxy-2-aminoindane (MEAI); Acute toxicity; Cytotoxicity; Ethanol; Subacute toxicity.

MeSH terms

  • Animals
  • Binge Drinking* / prevention & control
  • Binge Drinking* / psychology
  • Body Weight / drug effects*
  • Body Weight / physiology
  • Brain / drug effects
  • Brain / physiology
  • Drug Discovery / methods*
  • Drug Evaluation, Preclinical / methods
  • Female
  • Hepatocytes / drug effects
  • Hepatocytes / physiology
  • Humans
  • Indans / chemistry
  • Indans / therapeutic use
  • Indans / toxicity*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Toxicity Tests, Subacute / methods

Substances

  • Indans
  • 2-aminoindan