- "deconstruction" of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter
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Synthetic cathinones, β-keto analogues of amphetamine (or, more correctly, of phenylalkylamines), represent a new and growing class of abused substances. Several such analogues have been demonstrated to act as dopamine (DA) releasing agents. Methylenediox
- Kolanos, Renata,Solis, Ernesto,Sakloth, Farhana,De Felice, Louis J.,Glennon, Richard A.
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- Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships
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Rationale: The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated. Objective and methods: To study 3,4-methylenedioxypyrovalerone (MDPV; 3?mg/kg) and mephedrone (4-MMC; 30?mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal Emax modeling. Results: Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (p max (16.4 ± 5.5 versus 62.2 ± 14.2?μg/L, p 0 → ∞ (708 ± 91 versus 3316 ± 682?μg/L/min, p max model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC50, 0.043 versus 0.7?μmol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3. Conclusion: An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.
- Benturquia, Nadia,Chevillard, Lucie,Poiré, Christophe,Roussel, Olivier,Cohier, Camille,Declèves, Xavier,Laplanche, Jean-Louis,Etheve-Quelquejeu, Mélanie,Chen, Huixiong,Mégarbane, Bruno
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p. 891 - 901
(2018/07/13)
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- Preparation method and applications of methylenedioxypyrovalerone artificial antigen
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The invention provides a methylenedioxypyrovalerone artificial antigen preparation method, which comprises: preparing hapten, wherein a bromobutane Grignard reagent is prepared in anhydrous diethyl ether by using bromobutane and a metal magnesium as raw materials, methylenedioxypyrovalerone with hydroxyl linked on a pyrrole ring is prepared by using the bromobutane Grignard reagent and 3,4-methylenedioxybenzonitrile as raw materials through carbonylation, bromination and pyrrole alcohol amination, and finally hapten containing long arm carboxyl is prepared by carrying out a reaction on succinic anhydride and the hydroxyl on the pyrrole ring; and coupling the hapten and protein to synthesize artificial antigen, wherein the hapten and bovine serum albumin are coupled through a carbodiimide-catalyzed active ester process to prepare the methylenedioxypyrovalerone artificial antigen. According to the present invention, the prepared methylenedioxypyrovalerone artificial antigen can be used for immunizing animals to obtain corresponding antibodies so as to be used for the researches on various methylenedioxypyrovalerone immunoassay and be used as the key raw material for the production ofmethylenedioxypyrovalerone immunochromatographic kits.
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- Chiral resolution and absolute configuration of the enantiomers of the psychoactive designer drug 3,4-methylenedioxypyrovalerone
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Illicit rac-MDPV (3,4-methylenedioxypyrovalerone), manufactured in clandestine labs, has become widely abused for its cocaine-like stimulant properties. It has recently been found as one of the toxic materials in the so-called bath salts, producing, among other effects, psychosis and tachycardia in humans when introduced by any of the several routes of administration (e.g., intravenous, oral, etc.). The considerable toxicity of this designer drug probably resides in one of the enantiomers of the racemate. In order to obtain a sufficient amount of the enantiomers of rac-MDPV to determine their activity, we improved the known synthesis of rac-MDPV and found chemical resolving agents, (+)- and (-)-2'-bromotetranilic acid, that gave the MDPV enantiomers in >96% enantiomeric excess as determined by 1H nuclear magnetic resonance and chiral high-performance liquid chromatography. The absolute stereochemistry of these enantiomers was determined by single-crystal X-ray diffraction studies. Chirality 27:287-293, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
- Suzuki, Masaki,Deschamps, Jeffrey R.,Jacobson, Arthur E.,Rice, Kenner C.
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p. 287 - 293
(2015/03/30)
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- Immunoassay for pyrrolidinophenones
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The invention describes antibodies that bind molecules of the pyrrolidinophenone class of synthetic drugs. The antibodies are derived from novel chemical intermediates, haptens and immunogens and are used in methods and kits to detect and quantify pyrrolidinophenones.
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Paragraph 0025
(2013/08/28)
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- Synthesis and Insecticidal Activity of Sesquilignan Analogs with 2-Alkyl-6-methoxy-3-(3,4-methylenedioxyphenyl)-1,4-benzodioxanyl Group
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The methoxymethyl group of the 6-methoxy-2-methoxymethyl-3-(3,4-methylenedioxyphenyl)-1,4-benzodioxan-7-yl moiety of insecticidal lignans of Phryma was modified with several alkyl groups to evaluate the effect on activity of the substituents.The assay results make it evident that this activity was significantly modified by the chain length or bulkiness of the alkyl groups and that the oxygen atom of the methoxymethyl group was fairly important for enhancing the activity.
- Yamauchi, Satoshi,Taniguchi, Eiji
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p. 1751 - 1759
(2007/10/02)
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