Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F16%3A43914998" target="_blank" >RIV/00023752:_____/16:43914998 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11120/16:43911255 RIV/00216208:11110/16:10324364 RIV/60461373:22310/16:43901932 RIV/60461373:22330/16:43901932
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0278584616300513" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0278584616300513</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.pnpbp.2016.04.004" target="_blank" >10.1016/j.pnpbp.2016.04.004</a>
Alternative languages
Result language
angličtina
Original language name
Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats
Original language description
MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. We investigated a broad range of effects of acute MDAI administration 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 administration of 10 mg/kgMDAI; brain/serumratiowas ~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/kgMDAI 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. The drug had fast pharmacokinetics and accumulated in lipohilic tissues. Behavioural findings were consistent with mild, transient stimulationwith anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3,4- metyhlenedioxymethamphetamine and paramethoxymethamphetamine. Surprisingly subcutaneous MDAI appears to bemore lethal than previously thought and its serotonergic toxicity is likely exacerbated by group housing conditions. MDAI therefore poses greater risks to physical and mental health than recognised hitherto.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FH - Neurology, neuro-surgery, nuero-sciences
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Progress in Neuro-Psychopharmacology & Biological Psychiatry
ISSN
0278-5846
e-ISSN
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Volume of the periodical
69
Issue of the periodical within the volume
August 2016
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
49-59
UT code for WoS article
000376204500006
EID of the result in the Scopus database
2-s2.0-84964489810