Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: The effect of repeated administration of CAF (2 × 5 mg/kg), MDMA (4 × 10 mg/kg), and their combination on the extracellular level of DA and 5-HT in the mouse striatum. Time of drug injections is indicated with thick arrows. a , b Time-course. c , d Total effect expressed as an area under the curve (AUC). Values are presented as the mean ± SEM ( n = 4 animals per group). Basal extracellular levels of DA and 5-HT were as follows (pg/10 μl): control 1.18 ± 0.06 and 1.67 ± 0.25, CAF 1.42 ± 0.18 and 1.28 ± 0.18, MDMA 2.1 ± 0.23 and 1.27 ± 0.15, and MDMA plus CAF 1.92 ± 0.19 and 1.08 ± 0.09, respectively. * P < 0.0002 vs. control group; “a,” < 0.0002 difference vs. MDMA; “b,” < 0.002 difference vs. CAF ( a , b Repeated-measure ANOVA. c , d One-way ANOVA and Tukey’s post hoc test)

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Control

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: The effect of CAF (10 mg/kg), MDMA (20 mg/kg), and their combination on the extracellular level of DA and 5-HT in the mouse striatum in animals treated chronically with saline (acute) or CAF, MDMA, and MDMA plus CAF (chronic). a – d Time-course. Values are presented as the mean ± SEM ( n = 4–8 animals per group). * P < 0.0002 represents a significant difference in comparison to the control group; “a,” < 0.002 difference between MDMA and MDMA plus CAF; “b,” < 0.0002 difference between CAF and MDMA plus CAF (repeated-measure ANOVA and Tukey’s post hoc test)

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Saline, Comparison, Control

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: A comparison of the response to a challenging dose of drugs in animals treated repeatedly with saline (control) or chronically with CAF, MDMA, and MDMA plus CAF with respect to the extracellular levels of DA and 5-HT in the mouse striatum

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Comparison, Saline, Control

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: Tissue content of DA, DOPAC, HVA, 5-HT, and 5-HIAA in the mouse striatum and frontal cortex measured 3 h after cessation of treatment with drugs

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Control

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: The density of dopamine transporter (DAT) and serotonin transporter (SERT) in the mouse striatum and frontal cortex measured after cessation of treatment with the drugs

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Control

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: The effect of acute treatment of animals with CAF (10 mg/kg), MDMA (20 mg/kg), and their combination ( a ) or chronic administration of CAF, MDMA, and MDMA plus CAF ( b ) on the oxidative damage of DNA in nuclei from the mouse cortex 2 months after cessation of treatment. Values are presented as the mean ± SEM ( n = 4–8 animals per group). Data represent an olive tail moment. Olive tail moment is defined as the product of the tail length and the fraction of total DNA in the tail. Tail moment incorporates a measure of both the smallest detectable size of migrating DNA (reflected in the comet tail length) and the number of damaged pieces (represented by the intensity of DNA in the tail). The loss of DNA integrity persisted 60 days after drug administration. * P < 0.01 in comparison to control, “a,” “b” < 0.01 in comparison to MDMA or CAF groups, respectively (one-way ANOVA and Tukey’s post hoc test)

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Comparison, Control

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: Quantitative real-time PCR analysis of PDYN ( a ) and PENK ( b ) gene expressions in the mouse striatum after chronic administration of CAF, MDMA, and MDMA plus CAF. Values are presented as the mean ± SEM ( n = 4–10 animals per group). Data represent mRNA levels with respect to the control group. * P < 0.05; ** P < 0.001 in comparison to control (one-way ANOVA and Tukey’s post hoc test)

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Real-time Polymerase Chain Reaction, Control, Comparison

Journal: Neurotoxicity Research

Article Title: Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

doi: 10.1007/s12640-017-9831-9

Figure Lengend Snippet: The effect of chronic administration of CAF, MDMA, and MDMA plus CAF on exploratory and locomotor activities in the open-field ( a ) and novel object recognition ( b ) tests. Values are presented as the mean ± SEM ( n = 10–20 animals per group). Bars represent the time of walking and number of crossings ( a ), and time of exploration of novel object ( b ). * P < 0.01 in comparison to control; “a,” “b” < 0.01 in comparison to MDMA or CAF groups, respectively (one way ANOVA and Tukey’s post hoc test)

Article Snippet: Caffeine (CAF), was obtained from Sigma-Aldrich (Poznań, Poland) while MDMA was purchased from Toronto Research Chemicals Inc. (Canada).

Techniques: Comparison, Control

Journal: Neurotoxicity Research

Article Title: Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats

doi: 10.1007/s12640-016-9654-0

Figure Lengend Snippet: The effect of 5-MeO-DIPT (2.5, 5, and 10 mg/kg), MDMA (5 mg/kg) and (±)DOI (2.5 mg/kg) on the oxidative damage of cortical DNA in nuclei from the rat cortex. Data represent an olive tail moment. Olive Tail moment is defined as the product of the tail length and the fraction of total DNA in the tail. Tail moment incorporates a measure of both the smallest detectable size of migrating DNA (reflected in the comet tail length) and the number of damaged pieces (represented by the intensity of DNA in the tail). Loss of DNA integrity persisted from 72 h to 60 days after drugs administration. * P < 0.01 in comparison to control group (one-way ANOVA and post hoc Tukey’s test)

Article Snippet: 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 3,4- methylenedioxymethamphetamine (MDMA), were purchased from Toronto Research Chemicals Inc. (Canada). (1-(2,5-dimethoxy-4-iodophenyl)-aminopropane) hydrochloride (±)DOI), 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) came from Sigma-Aldrich (Poland).

Techniques: Comparison, Control

Journal: Neurotoxicity Research

Article Title: Effect of Some Psychoactive Drugs Used as ‘Legal Highs’ on Brain Neurotransmitters

doi: 10.1007/s12640-015-9569-1

Figure Lengend Snippet: Effect of MDMA on DA release in rat striatum, nucleus accumbens, and frontal cortex. Data are mean ± SEM ( n = 4–5). Drug administration is indicated with an arrow. Basal extracellular level of DA (pg/10 μl) was 18.7 ± 1.0 (striatum); 1.01 ± 0.14 (n. accumbens); and 1.02 ± 0.24 (frontal cortex). * P < 0.01 in comparison to control group (repeated measures ANOVA and Tukey’s post hoc test)

Article Snippet: 3,4-Methylenedioxymethamphetamine (MDMA), 4-methoxyamphetamine (PMA), and 4-methoxy- N -methylamphetamine (PMMA) were purchased from Toronto Research Chemicals Inc. (Canada). (±)-4-Methylmethcathinone (mephedrone) was purchased from Chemwatch (Australia).

Techniques: Comparison, Control

Journal: Neurotoxicity Research

Article Title: Effect of Some Psychoactive Drugs Used as ‘Legal Highs’ on Brain Neurotransmitters

doi: 10.1007/s12640-015-9569-1

Figure Lengend Snippet: Effect of MDMA on 5-HT release in rat striatum, nucleus accumbens, and frontal cortex. Data are mean ± SEM ( n = 4–5). Drug administration is indicated with an arrow. Basal extracellular level of 5-HT (pg/10 μl) was 0.51 ± 0.14 (striatum); 0.19 ± 0.04 (n. accumbens); and 0.22 ± 0.03 (frontal cortex). * P < 0.01 in comparison to control group (repeated measures ANOVA and Tukey’s post hoc test)

Article Snippet: 3,4-Methylenedioxymethamphetamine (MDMA), 4-methoxyamphetamine (PMA), and 4-methoxy- N -methylamphetamine (PMMA) were purchased from Toronto Research Chemicals Inc. (Canada). (±)-4-Methylmethcathinone (mephedrone) was purchased from Chemwatch (Australia).

Techniques: Comparison, Control

Journal: Neurotoxicity Research

Article Title: Effect of Some Psychoactive Drugs Used as ‘Legal Highs’ on Brain Neurotransmitters

doi: 10.1007/s12640-015-9569-1

Figure Lengend Snippet: Total effect of PMA, PMMA, mephedrone (MEPH), and MDMA at a dose of 10 mg/kg on DA and 5-HT release in the rat striatum, n. accumbens, and the frontal cortex

Article Snippet: 3,4-Methylenedioxymethamphetamine (MDMA), 4-methoxyamphetamine (PMA), and 4-methoxy- N -methylamphetamine (PMMA) were purchased from Toronto Research Chemicals Inc. (Canada). (±)-4-Methylmethcathinone (mephedrone) was purchased from Chemwatch (Australia).

Techniques: Control

Journal: bioRxiv

Article Title: Bioisosteric analogs of MDMA with improved pharmacological profile

doi: 10.1101/2024.04.08.588083

Figure Lengend Snippet: (A) Chemical structures of MDMA and its analogs ODMA, TDMA, and SeDMA, in which the methylenedioxy group or its chemical modification is highlighted in red, blue, purple, or green, respectively; (B) Uptake inhibition curves at hSERT (left panel) and hDAT (right panel). Curves were plotted and fitted by non-linear regression, and data were best fitted to a sigmoidal dose-response curve to obtain IC 50 values ; (C) Transporter-mediated release (batch) of preloaded [ 3 H]5-HT from HEK293 cells stably expressing hSERT. Compounds were added at a concentration close to their IC 50 value (MDMA (14 µM), ODMA (23 µM), TDMA (7 µM), SeDMA (20 µM)) from 8 to 18 min, either in KHB (empty symbols) or in KHB+Mon (10 μM) (filled symbols); (D) Transporter-mediated release (superfusion) of preloaded [ 3 H]MPP + from HEK293 cells stably expressing hDAT. Similarly, compounds were added at a concentration close to their IC 50 value (MDMA, ODMA, and TDMA (6 µM), SeDMA (10 µM)) from 8 to 18 min either in KHB (empty symbols) or in KHB+Mon (10 μM) (filled symbols); (E) Illustrative representation of [ 3 H]5-HT reverse transport at hSERT (left panel; created with BioRender.com ) and the calculated area under the curve between 8 and 18 minutes (AUC 8-18min ) of the [ 3 H]5-HT released by each compound in KHB (-) or KHB+Mon (+) conditions (right panel) (MDMA KHB = 108.9 ± 34.0 vs. MDMA MON = 282.3 ± 15.4; ODMA KHB = 81.5 ± 20.9 vs. ODMA MON = 240.3 ± 19.3; TDMA KHB = 60.2 ± 20.0 vs. TDMA MON = 227.9 ± 53.4; SeDMA KHB = 96.0 ± 1.7 vs. SeDMA MON = 279.2 ± 9.3); ( F ) Illustrative representation of [ 3 H]MPP + reverse transport at hDAT (left panel; created with BioRender.com ) and the calculated AUC 8-18min of the [ 3 H]MPP + released by each compound in KHB (-) or KHB+Mon (+) conditions (right panel) (MDMA KHB = 33.3 ± 7.5 vs. MDMA MON = 63.1 ± 9.3; ODMA KHB = 44.5 ± 5.5 vs. ODMA MON = 63.1 ± 13.0; TDMA KHB = 28.9 ± .6.6 vs. TDMA MON = 49.4 ± 9.7; SeDMA KHB = 31.6 ± 5.5 vs. SeDMA MON = 52.9 ± 5.9). Data are mean ± SD from three to five individual experiments, performed in triplicate (uptake inhibition assays and superfusion release assays) or duplicate (batch release assays). Statistical analyses explored possible significant differences between KHB and KHB+Mon conditions. Statistical significance was defined at a p-value lower than 0.05. *denotes p<0.05, **p<0.01, and ***p<0.001.

Article Snippet: The experimental drug MDMA hydrochloride (HCl) (MW = 229.7 g/mol) was purchased from Lipomed AG (Arlesheim, Switzerland) or Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Modification, Inhibition, Stable Transfection, Expressing, Concentration Assay

Journal: bioRxiv

Article Title: Bioisosteric analogs of MDMA with improved pharmacological profile

doi: 10.1101/2024.04.08.588083

Figure Lengend Snippet: ( A ) Representative single-cell traces showing hSERT-mediated currents elicited by increasing concentration of 5-HT (grey), MDMA (red), ODMA (blue), TDMA (purple), and SeDMA (green); ( B ) Concentration-response curves at hSERT. Data were normalized to the steady-state current of the saturating concentration of 5-HT (10 µM) and plotted using non-linear regression. The EC 50 values were extrapolated (5-HT: 0.17 µM < MDMA: 0.27 µM < TDMA: 0.44 µM < SeDMA: 0.77 µM < ODMA: 1.27 µM) as well as the E MAX values (5-HT: 94%; MDMA: 92.6%; TDMA: 93.2%; SeDMA 97.1%; ODMA: 109.5%); ( C ) Representative single-cell traces showing hDAT-mediated currents elicited by increasing concentration of DA (grey), MDMA (red), ODMA (blue), TDMA (purple), and SeDMA (green); ( D ) Concentration-response curves at hDAT. Data were normalized to the steady-state current of the saturating concentration of DA (30 µM) and plotted using non-linear regression. The EC 50 values were extrapolated (MDMA: 2.51 µM < ODMA: 3.97 µM < TDMA: 4.29 µM < SeDMA: 5.97 µM < DA: 6.40 µM) as well as the E MAX values (DA: 104.1%; MDMA: 31.9%; ODMA: 48.2%; TDMA: 30.1%; SeDMA: 25.7%). Data are mean ± SD from two to seven individual cells per each concentration.

Article Snippet: The experimental drug MDMA hydrochloride (HCl) (MW = 229.7 g/mol) was purchased from Lipomed AG (Arlesheim, Switzerland) or Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Concentration Assay

Journal: bioRxiv

Article Title: Bioisosteric analogs of MDMA with improved pharmacological profile

doi: 10.1101/2024.04.08.588083

Figure Lengend Snippet: ( A, C ) Outward-open structure of hSERT (purple) or hDAT (green cyan) and the binding poses of all ligands in each transporter. MDMA: salmon, OMDA: blue, TMDA: purple, SeDMA: green and both and serotonin (5-HT) and dopamine (DA) in light grey; ( B ) Left and right panels show the 2D interaction scheme of MDMA and TDMA molecules, respectively, highlighting the main interactions with hSERT (obtained using Maestro version 13.6.122); ( D ) Left and right panels show the 2D interaction scheme of MDMA and TDMA molecules, respectively, highlighting the main interactions with hDAT (obtained using Maestro version 13.6.122). The asterisks indicate the residues that also interact with 5-HT in hSERT (PDB ID:7MGW) and with DA in dDAT (PDB ID:4XP1). The residues of the protein are shown like guitar picks linked together on a string. The orientation of the guitar pick must be read as: the guitar picks pointing away from the ligand means the backbone of that residue is facing towards the ligand, and when the guitar pick is pointing toward the ligand that means the side chain of that residue facing the ligand.

Article Snippet: The experimental drug MDMA hydrochloride (HCl) (MW = 229.7 g/mol) was purchased from Lipomed AG (Arlesheim, Switzerland) or Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Binding Assay, Residue

Journal: bioRxiv

Article Title: Bioisosteric analogs of MDMA with improved pharmacological profile

doi: 10.1101/2024.04.08.588083

Figure Lengend Snippet: ( A ) BRET Gq dissociation assay for human 5-HT2 receptors (5-HT 2A -green, 5-HT 2B -red, 5-HT 2C -blue) using (B) 5-HT as positive control and measuring agonist activity of (C) MDMA compared to MDMA bioisosteric analogs (D) ODMA, (E) TDMA and (F) SeDMA. Data represent mean and SEM from three independent experiments.

Article Snippet: The experimental drug MDMA hydrochloride (HCl) (MW = 229.7 g/mol) was purchased from Lipomed AG (Arlesheim, Switzerland) or Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Positive Control, Activity Assay

Journal: bioRxiv

Article Title: Bioisosteric analogs of MDMA with improved pharmacological profile

doi: 10.1101/2024.04.08.588083

Figure Lengend Snippet: ( A-C ) Metabolic pathways of ODMA, TDMA, and SeDMA in incubations with pooled human liver microsomes. Undefined hydroxylation position is indicated by unspecific bonds. Metabolite-IDs correspond to ; ( D ) Metabolic pathways of MDMA reported in literature in incubations with pooled human liver microsomes and/or S9 fraction ( Richter et al . 2017a ; Schwaninger et al . 2011b ). Metabolite-IDs correspond to ; ( E ) Uptake-inhibition curves at hOCT1, hOCT2, hOCT3, and hPMAT. Curves were plotted and fitted by non-linear regression, and data were best fitted to a sigmoidal dose-response curve to obtain IC 50 values (see ). Data are mean ± SD for individual experiments, performed in triplicate (n=3-4).

Article Snippet: The experimental drug MDMA hydrochloride (HCl) (MW = 229.7 g/mol) was purchased from Lipomed AG (Arlesheim, Switzerland) or Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Inhibition