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John Corkery - One of the best experts on this subject based on the ideXlab platform.
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MDAI (5,6‐methylenedioxy‐2‐aminoindane; 6,7‐dihydro‐5H‐cyclopenta[f][1,3]benzodioxol‐6‐amine; ‘sparkle’; ‘mindy’) toxicity: a brief overview and update
Human Psychopharmacology-clinical and Experimental, 2013Co-Authors: John Corkery, Simon Elliott, Fabrizio Schifano, Ornella Corazza, A. Hamid GhodseAbstract:OBJECTIVES: MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') is a psychoactive substance, sold primarily over the Internet and in 'head' shops as a 'legal high'. Synthesised and used as a research chemical in the 1990s, MDAI has structural similarities to MDMA (3,4-methylenedioxy-N-methylamphetamine) and shares its behavioural properties. Recreational use of MDAI appears to have started in Europe around 2007, with a noticeable increase after 2009 in the UK and other countries. Calls to National Poisons Information Services started in 2010, although there were few presentations to emergency departments by patients complaining of undesirable physical and psychiatric effects after taking MDAI. Recreational use of this drug has been reported only occasionally by online user fora. There is little scientifically based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of this drug. METHODS: Recent literature (including 'grey') was searched to update what is known about MDAI, especially on its toxicity. RESULTS: The resultant information is presented, including on the first three UK deaths involving MDAI use in 2011 and 2012. 'Serotonin syndrome' appears to be a possible factor in these fatalities. CONCLUSION: It is vital that any other cases, including non-fatal overdoses, are documented so that a scientific evidence base can be established for them. Copyright © 2013 John Wiley & Sons, Ltd. Language: en
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MDAI 5 6 methylenedioxy 2 aminoindane 6 7 dihydro 5h cyclopenta f 1 3 benzodioxol 6 amine sparkle mindy toxicity a brief overview and update
Human Psychopharmacology-clinical and Experimental, 2013Co-Authors: John Corkery, Simon Elliott, Fabrizio Schifano, Ornella Corazza, Hamid A GhodseAbstract:OBJECTIVES: MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') is a psychoactive substance, sold primarily over the Internet and in 'head' shops as a 'legal high'. Synthesised and used as a research chemical in the 1990s, MDAI has structural similarities to MDMA (3,4-methylenedioxy-N-methylamphetamine) and shares its behavioural properties. Recreational use of MDAI appears to have started in Europe around 2007, with a noticeable increase after 2009 in the UK and other countries. Calls to National Poisons Information Services started in 2010, although there were few presentations to emergency departments by patients complaining of undesirable physical and psychiatric effects after taking MDAI. Recreational use of this drug has been reported only occasionally by online user fora. There is little scientifically based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of this drug. METHODS: Recent literature (including 'grey') was searched to update what is known about MDAI, especially on its toxicity. RESULTS: The resultant information is presented, including on the first three UK deaths involving MDAI use in 2011 and 2012. 'Serotonin syndrome' appears to be a possible factor in these fatalities. CONCLUSION: It is vital that any other cases, including non-fatal overdoses, are documented so that a scientific evidence base can be established for them. Copyright © 2013 John Wiley & Sons, Ltd. Language: en
Monika židkova - One of the best experts on this subject based on the ideXlab platform.
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study on the metabolism of 5 6 methylenedioxy 2 aminoindane MDAI in rats identification of urinary metabolites
Xenobiotica, 2017Co-Authors: Monika židkova, Tomas Palenicek, Eva Lhotkova, Marie Balikova, Michal Himl, Igor Linhart, Lubomir Vaňa, Michal Vetýska, Martin DusekAbstract:Abstract1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs.2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS.3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged.4. Minor metabo...
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emerging toxicity of 5 6 methylenedioxy 2 aminoindane MDAI pharmacokinetics behaviour thermoregulation and ld50 in rats
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2016Co-Authors: Tomas Palenicek, Eva Lhotkova, Monika židkova, Marie Balikova, Martin Kuchař, Michal Himl, Petra Miksatkova, Martin Cegan, Karel Vales, F TylsAbstract:Abstract 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. 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 (median lethal dose, LD50) 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 ~ 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 (DIC) 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. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3,4-metyhlenedioxymethamphetamine (MDMA, ecstasy) and paramethoxymethamphetamine (PMMA). Surprisingly subcutaneous MDAI appears to be more 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.
Tomas Palenicek - One of the best experts on this subject based on the ideXlab platform.
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study on the metabolism of 5 6 methylenedioxy 2 aminoindane MDAI in rats identification of urinary metabolites
Xenobiotica, 2017Co-Authors: Monika židkova, Tomas Palenicek, Eva Lhotkova, Marie Balikova, Michal Himl, Igor Linhart, Lubomir Vaňa, Michal Vetýska, Martin DusekAbstract:Abstract1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs.2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS.3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged.4. Minor metabo...
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emerging toxicity of 5 6 methylenedioxy 2 aminoindane MDAI pharmacokinetics behaviour thermoregulation and ld50 in rats
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2016Co-Authors: Tomas Palenicek, Eva Lhotkova, Monika židkova, Marie Balikova, Martin Kuchař, Michal Himl, Petra Miksatkova, Martin Cegan, Karel Vales, F TylsAbstract:Abstract 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. 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 (median lethal dose, LD50) 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 ~ 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 (DIC) 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. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3,4-metyhlenedioxymethamphetamine (MDMA, ecstasy) and paramethoxymethamphetamine (PMMA). Surprisingly subcutaneous MDAI appears to be more 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.
Martin Dusek - One of the best experts on this subject based on the ideXlab platform.
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study on the metabolism of 5 6 methylenedioxy 2 aminoindane MDAI in rats identification of urinary metabolites
Xenobiotica, 2017Co-Authors: Monika židkova, Tomas Palenicek, Eva Lhotkova, Marie Balikova, Michal Himl, Igor Linhart, Lubomir Vaňa, Michal Vetýska, Martin DusekAbstract:Abstract1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs.2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS.3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged.4. Minor metabo...
Eva Lhotkova - One of the best experts on this subject based on the ideXlab platform.
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study on the metabolism of 5 6 methylenedioxy 2 aminoindane MDAI in rats identification of urinary metabolites
Xenobiotica, 2017Co-Authors: Monika židkova, Tomas Palenicek, Eva Lhotkova, Marie Balikova, Michal Himl, Igor Linhart, Lubomir Vaňa, Michal Vetýska, Martin DusekAbstract:Abstract1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs.2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS.3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged.4. Minor metabo...
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emerging toxicity of 5 6 methylenedioxy 2 aminoindane MDAI pharmacokinetics behaviour thermoregulation and ld50 in rats
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2016Co-Authors: Tomas Palenicek, Eva Lhotkova, Monika židkova, Marie Balikova, Martin Kuchař, Michal Himl, Petra Miksatkova, Martin Cegan, Karel Vales, F TylsAbstract:Abstract 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. 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 (median lethal dose, LD50) 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 ~ 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 (DIC) 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. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3,4-metyhlenedioxymethamphetamine (MDMA, ecstasy) and paramethoxymethamphetamine (PMMA). Surprisingly subcutaneous MDAI appears to be more 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.