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Jeanlouis Laplanche - One of the best experts on this subject based on the ideXlab platform.
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the neurobehavioral effects of the designer drug Naphyrone an experimental investigation with pharmacokinetics and concentration effect relationship in mice
Psychopharmacology, 2020Co-Authors: Bruno Megarbane, Camille Gamblin, Olivier Roussel, Elodie Bouazizamar, Lucie Chevillard, Jacques Callebert, Huixiong Chen, Gilles Morineau, Jeanlouis LaplancheAbstract:RATIONALE The recreational use of Naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. OBJECTIVE To investigate Naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. METHODS We studied Naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal Naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled Naphyrone pharmacokinetics and concentration/locomotor effect relationship. RESULTS Both Naphyrone administration patterns induced time-dependent increases in locomotor activity (p < 0.001 and p < 0.0001, respectively) and social interaction (p < 0.05 and p < 0.001, respectively) but did not alter spatial recognition memory or anhedonia. Acute Naphyrone injection induced anxiety-like behavior (p < 0.01) and reduced resignation (p < 0.01) whereas binge administration induced non-anxiety-like behavior (p < 0.05) and did not alter behavioral despair. Both patterns increased the prefrontal cortex dopamine (p < 0.0001) and norepinephrine (p < 0.05 and p < 0.01, respectively) but not serotonin content. Naphyrone pharmacokinetics followed a two-compartment model with an overall elimination half-life of 0.3 h. The Naphyrone concentration/locomotor effect relationship was described by an additive Emax model with an EC50 of 672 μg/L. CONCLUSIONS Single Naphyrone administration increases locomotor activity according to a direct concentration/effect relationship. The neurobehavioral effects after binge differs from those after single administration and are not explained by drug accumulation given the relatively fast elimination.
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the neurobehavioral effects of the designer drug Naphyrone an experimental investigation with pharmacokinetics and concentration effect relationship in mice
Psychopharmacology, 2020Co-Authors: Bruno Megarbane, Camille Gamblin, Olivier Roussel, Elodie Bouazizamar, Lucie Chevillard, Jacques Callebert, Huixiong Chen, Gilles Morineau, Jeanlouis LaplancheAbstract:The recreational use of Naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. To investigate Naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. We studied Naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal Naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled Naphyrone pharmacokinetics and concentration/locomotor effect relationship. Both Naphyrone administration patterns induced time-dependent increases in locomotor activity (p < 0.001 and p < 0.0001, respectively) and social interaction (p < 0.05 and p < 0.001, respectively) but did not alter spatial recognition memory or anhedonia. Acute Naphyrone injection induced anxiety-like behavior (p < 0.01) and reduced resignation (p < 0.01) whereas binge administration induced non-anxiety-like behavior (p < 0.05) and did not alter behavioral despair. Both patterns increased the prefrontal cortex dopamine (p < 0.0001) and norepinephrine (p < 0.05 and p < 0.01, respectively) but not serotonin content. Naphyrone pharmacokinetics followed a two-compartment model with an overall elimination half-life of 0.3 h. The Naphyrone concentration/locomotor effect relationship was described by an additive Emax model with an EC50 of 672 μg/L. Single Naphyrone administration increases locomotor activity according to a direct concentration/effect relationship. The neurobehavioral effects after binge differs from those after single administration and are not explained by drug accumulation given the relatively fast elimination.
Olivier Roussel - One of the best experts on this subject based on the ideXlab platform.
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the neurobehavioral effects of the designer drug Naphyrone an experimental investigation with pharmacokinetics and concentration effect relationship in mice
Psychopharmacology, 2020Co-Authors: Bruno Megarbane, Camille Gamblin, Olivier Roussel, Elodie Bouazizamar, Lucie Chevillard, Jacques Callebert, Huixiong Chen, Gilles Morineau, Jeanlouis LaplancheAbstract:RATIONALE The recreational use of Naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. OBJECTIVE To investigate Naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. METHODS We studied Naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal Naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled Naphyrone pharmacokinetics and concentration/locomotor effect relationship. RESULTS Both Naphyrone administration patterns induced time-dependent increases in locomotor activity (p < 0.001 and p < 0.0001, respectively) and social interaction (p < 0.05 and p < 0.001, respectively) but did not alter spatial recognition memory or anhedonia. Acute Naphyrone injection induced anxiety-like behavior (p < 0.01) and reduced resignation (p < 0.01) whereas binge administration induced non-anxiety-like behavior (p < 0.05) and did not alter behavioral despair. Both patterns increased the prefrontal cortex dopamine (p < 0.0001) and norepinephrine (p < 0.05 and p < 0.01, respectively) but not serotonin content. Naphyrone pharmacokinetics followed a two-compartment model with an overall elimination half-life of 0.3 h. The Naphyrone concentration/locomotor effect relationship was described by an additive Emax model with an EC50 of 672 μg/L. CONCLUSIONS Single Naphyrone administration increases locomotor activity according to a direct concentration/effect relationship. The neurobehavioral effects after binge differs from those after single administration and are not explained by drug accumulation given the relatively fast elimination.
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the neurobehavioral effects of the designer drug Naphyrone an experimental investigation with pharmacokinetics and concentration effect relationship in mice
Psychopharmacology, 2020Co-Authors: Bruno Megarbane, Camille Gamblin, Olivier Roussel, Elodie Bouazizamar, Lucie Chevillard, Jacques Callebert, Huixiong Chen, Gilles Morineau, Jeanlouis LaplancheAbstract:The recreational use of Naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. To investigate Naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. We studied Naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal Naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled Naphyrone pharmacokinetics and concentration/locomotor effect relationship. Both Naphyrone administration patterns induced time-dependent increases in locomotor activity (p < 0.001 and p < 0.0001, respectively) and social interaction (p < 0.05 and p < 0.001, respectively) but did not alter spatial recognition memory or anhedonia. Acute Naphyrone injection induced anxiety-like behavior (p < 0.01) and reduced resignation (p < 0.01) whereas binge administration induced non-anxiety-like behavior (p < 0.05) and did not alter behavioral despair. Both patterns increased the prefrontal cortex dopamine (p < 0.0001) and norepinephrine (p < 0.05 and p < 0.01, respectively) but not serotonin content. Naphyrone pharmacokinetics followed a two-compartment model with an overall elimination half-life of 0.3 h. The Naphyrone concentration/locomotor effect relationship was described by an additive Emax model with an EC50 of 672 μg/L. Single Naphyrone administration increases locomotor activity according to a direct concentration/effect relationship. The neurobehavioral effects after binge differs from those after single administration and are not explained by drug accumulation given the relatively fast elimination.
Juliet Kinyua - One of the best experts on this subject based on the ideXlab platform.
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Liquid chromatography-tandem mass spectrometry determination of synthetic cathinones and phenethylamines in influent wastewater of eight European cities.
Chemosphere, 2017Co-Authors: Richard Bade, Lubertus Bijlsma, Juan V. Sancho, Jose Antonio Baz-lomba, Sara Castiglioni, Erika Castrignanò, Ana Causanilles, Emma Gracia-lor, Barbara Kasprzyk-hordern, Juliet KinyuaAbstract:The popularity of new psychoactive substances (NPS) has grown in recent years, with certain NPS commonly and preferentially consumed even following the introduction of preventative legislation. With the objective to improve the knowledge on the use of NPS, a rapid and very sensitive method was developed for the determination of ten priority NPS (N-ethylcathinone, methylenedioxypyrovalerone (MDPV), methylone, butylone, methedrone, mephedrone, Naphyrone, 25-C-NBOMe, 25-I-NBOMe and 25-B-NBOMe) in influent wastewater. Sample clean-up and pre-concentration was made by off-line solid phase extraction (SPE) with Oasis MCX cartridges. Isotopically labelled internal standards were used to correct for matrix effects and potential SPE losses. Following chromatographic separation on a C18 column within 6 min, the compounds were measured by tandem mass spectrometry in positive ionization mode. The method was optimised and validated for all compounds. Limits of quantification were evaluated by spiking influent wastewater samples at 1 or 5 ng/L. An investigation into the stability of these compounds in influent wastewater was also performed, showing that, following acidification at pH 2, all compounds were relatively stable for up to 7 days. The method was then applied to influent wastewater samples from eight European countries, in which mephedrone, methylone and MDPV were detected. This work reveals that although NPS use is not as extensive as for classic illicit drugs, the application of a highly sensitive analytical procedure makes their detection in wastewater possible. The developed analytical methodology forms the basis of a subsequent model-based back-calculation of abuse rate in urban areas (i.e. wastewater-based epidemiology).
Katharina M. Rentsch - One of the best experts on this subject based on the ideXlab platform.
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Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS(n), and metabolism of 11 cathinones
Analytical and Bioanalytical Chemistry, 2012Co-Authors: Daniel M. Mueller, Katharina M. RentschAbstract:Human liver microsomes (HLMs) are used to simulate human xenobiotic metabolism in vitro. In forensic and clinical toxicology, HLMs are popularly used to study the metabolism of new designer drugs for example. In this work, we present an automated online extraction system we developed for HLM experiments, which was compared to a classical offline approach. Furthermore, we present studies on the metabolism of 11 cathinones; for eight of these, the metabolism has not previously been reported. Metabolites were identified based on MS^2 and MS^3 scans. Fifty-three substances encompassing various classes of drugs were employed to compare the established offline and the new online methods. The metabolism of each of the following 11 cathinones was studied using the new method: 3,4-methylenedioxy- N -benzylcathinone, benzedrone, butylone, dimethylcathinone, ethylone, flephedrone, methedrone, methylone, methylethylcathinone, Naphyrone, and pentylone. The agreement between the offline and the online methods was good; a total of 158 metabolites were identified. Using only the offline method, 156 (98.7%) metabolites were identified, while 151 (95.6%) were identified using only the online method. The metabolic pathways identified for the 11 cathinones included the reduction of the keto group, desalkylation, hydroxylation, and desmethylenation in cathinones containing a methylenedioxy moiety. Our method provides a straightforward approach to identifying metabolites which can then be added to the library utilized by our clinical toxicological screening method. The performance of our method compares well with that of an established offline HLM procedure, but is as automated as possible.
Bruno Megarbane - One of the best experts on this subject based on the ideXlab platform.
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the neurobehavioral effects of the designer drug Naphyrone an experimental investigation with pharmacokinetics and concentration effect relationship in mice
Psychopharmacology, 2020Co-Authors: Bruno Megarbane, Camille Gamblin, Olivier Roussel, Elodie Bouazizamar, Lucie Chevillard, Jacques Callebert, Huixiong Chen, Gilles Morineau, Jeanlouis LaplancheAbstract:RATIONALE The recreational use of Naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. OBJECTIVE To investigate Naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. METHODS We studied Naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal Naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled Naphyrone pharmacokinetics and concentration/locomotor effect relationship. RESULTS Both Naphyrone administration patterns induced time-dependent increases in locomotor activity (p < 0.001 and p < 0.0001, respectively) and social interaction (p < 0.05 and p < 0.001, respectively) but did not alter spatial recognition memory or anhedonia. Acute Naphyrone injection induced anxiety-like behavior (p < 0.01) and reduced resignation (p < 0.01) whereas binge administration induced non-anxiety-like behavior (p < 0.05) and did not alter behavioral despair. Both patterns increased the prefrontal cortex dopamine (p < 0.0001) and norepinephrine (p < 0.05 and p < 0.01, respectively) but not serotonin content. Naphyrone pharmacokinetics followed a two-compartment model with an overall elimination half-life of 0.3 h. The Naphyrone concentration/locomotor effect relationship was described by an additive Emax model with an EC50 of 672 μg/L. CONCLUSIONS Single Naphyrone administration increases locomotor activity according to a direct concentration/effect relationship. The neurobehavioral effects after binge differs from those after single administration and are not explained by drug accumulation given the relatively fast elimination.
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the neurobehavioral effects of the designer drug Naphyrone an experimental investigation with pharmacokinetics and concentration effect relationship in mice
Psychopharmacology, 2020Co-Authors: Bruno Megarbane, Camille Gamblin, Olivier Roussel, Elodie Bouazizamar, Lucie Chevillard, Jacques Callebert, Huixiong Chen, Gilles Morineau, Jeanlouis LaplancheAbstract:The recreational use of Naphyrone, a potent synthetic cathinone with a pyrovalerone structure, has raised questions about possible deleterious neurobehavioral consequences. To investigate Naphyrone-induced neurobehavioral effects and alterations in brain monoamines using two patterns of abuse, i.e., single and repeated (binge) use. We studied Naphyrone dose/induced locomotor activity relationship at 3, 10, 30, and 100 mg/kg in mice. We investigated the effects of single (30 mg/kg; acute injection) versus repeated (30 mg/kg ×3/day for 3 days; binge injection) intraperitoneal Naphyrone administration on locomotor activity, anxiety-like behavior, spatial recognition memory, anhedonia, behavioral despair, and social interaction. We measured post-mortem prefrontal cortex levels of monoamines and modeled Naphyrone pharmacokinetics and concentration/locomotor effect relationship. Both Naphyrone administration patterns induced time-dependent increases in locomotor activity (p < 0.001 and p < 0.0001, respectively) and social interaction (p < 0.05 and p < 0.001, respectively) but did not alter spatial recognition memory or anhedonia. Acute Naphyrone injection induced anxiety-like behavior (p < 0.01) and reduced resignation (p < 0.01) whereas binge administration induced non-anxiety-like behavior (p < 0.05) and did not alter behavioral despair. Both patterns increased the prefrontal cortex dopamine (p < 0.0001) and norepinephrine (p < 0.05 and p < 0.01, respectively) but not serotonin content. Naphyrone pharmacokinetics followed a two-compartment model with an overall elimination half-life of 0.3 h. The Naphyrone concentration/locomotor effect relationship was described by an additive Emax model with an EC50 of 672 μg/L. Single Naphyrone administration increases locomotor activity according to a direct concentration/effect relationship. The neurobehavioral effects after binge differs from those after single administration and are not explained by drug accumulation given the relatively fast elimination.
