Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11120/16:43911255 RIV/00216208:11110/16:10324364 RIV/60461373:22310/16:43901932 RIV/60461373:22330/16:43901932

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Progress in Neuro-Psychopharmacology &amp; Biological Psychiatry

ISSN

0278-5846

e-ISSN

—

Svazek periodika

69

Číslo periodika v rámci svazku

August 2016

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

49-59

Kód UT WoS článku

000376204500006

EID výsledku v databázi Scopus

2-s2.0-84964489810