Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats
Abstract
MDAI has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity in Wistar rats.
Pharmacokinetics of MDAI was rapid, maximum median concentration in serum and brain was attained 30 min and almost returned to zero 6 h after subcutaneous (sc.) administration of 10 mg/kg MDAI; brain/serum ratio was similar to 4. MDAI particularly accumulated in lung tissue.
In the open field, MDAI (5, 10, 20 and 40 mg/kg sc.) increased exploratory activity, induced signs of behavioural serotonin syndrome and reduced locomotor habituation, although by 60 min some effects had diminished. All doses of MDAI significantly disrupted PPI and the effect was present during the onset of its action as well as 60 min after treatment.
Unexpectedly, 40 mg/kg MDAI killed 90% of animals in the first behavioural test, hence LD50 tests were conducted which yielded 28.33 mg/kg sc. and 35 mg/kg intravenous but was not established up to 40 mg/kg after gastric administration. Disseminated intravascular coagulopathy with brain oedema was concluded as a direct cause of death in sc. treated animals.
Finally, MDAI (10, 20 mg/kg sc.) caused hyperthermia and perspiration in group-housed rats. In conclusion, the drug had fast pharmacokinetics and accumulated in lipohilic tissues.