Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development.
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 IC50value 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.
Kimron Veterinary Institute, Department of Toxicology, Bet Dagan, Israel. Electronic address: jakobshimshoni@gmail.com.
Jakob A
JA
Shimshoni
Pharmaseed Ltd, Ness Ziona, Israel.
Ilan
I
Winkler
Kimron Veterinary Institute, Department of Pathology, Bet Dagan, Israel.
Nir
N
Edery
BSC BV Company, Veemarkt 61, Amsterdam, The Netherland.
Ezekiel
E
Golan
BSC BV Company, Veemarkt 61, Amsterdam, The Netherland.
René
R
van Wettum
Imperial College London, Neuropsychopharmacology Unit, London, UK.
David
D
Nutt
D000818:Animals; D063425:Binge Drinking / Q000517:prevention & control / Q000523:psychology; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D059551:Toxicity Tests, Subacute / Q000379:methods
D007189:Indans; C006545:2-aminoindan
5-Methoxy-2-aminoindane (MEAI); Acute toxicity; Cytotoxicity; Ethanol; Subacute toxicity