New designer drug α-pyrrolidinovalerophenone (PVP): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. J Mass Spectrom

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421 Homburg (Saar), Germany.
Journal of Mass Spectrometry (Impact Factor: 2.38). 06/2009; 44(6):952-64. DOI: 10.1002/jms.1571
Source: PubMed


The aim of the present study was to identify the metabolites of the new designer drug alpha-pyrrolidinovalerophenone (PVP) in rat urine using GC/MS techniques. Eleven metabolites of PVP could be identified suggesting the following metabolic steps: hydroxylation of the side chain followed by dehydrogenation to the corresponding ketone; hydroxylation of the 2''-position of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam or followed by ring opening to the respective aliphatic aldehyde and further oxidation to the respective carboxylic acid; degradation of the pyrrolidine ring to the corresponding primary amine; and hydroxylation of the phenyl ring, most probably in the 4'-position. The authors' screening procedure for pyrrolidinophenones allowed the detection of PVP metabolites after application of a dose corresponding to a presumed user's dose. In addition, the involvement of nine different human cytochrome P450 (CYP) isoenzymes in the side chain hydroxylation of PVP was investigated and CYP 2B6, 2C19, 2D6, and 3A4 were found to catalyze this reaction.

    • "Cathinone is a monoamine alkaloid found in the shrub Catha edulis (khat). Most of the synthetic cathinone supply originates in China or India and spreads worldwide (Sauer et al., 2009; Marinetti and Antonides, 2013). Cathinone and its derivatives synthetic cathinones are structurally similar to ephedrine, cathine and other phenylethylamines ; therefore, their properties closely resemble those of amphetamine (Glennon et al., 1987; Kalix et al., 1992; Widler et al., 1994; Cozzi et al., 1999). "
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    ABSTRACT: 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) is a new designer drug of the cathinone type. People who have taken drugs containing α-PVP or other synthetic cathinone reportedly lose consciousness, develop difficulty breathing, and at worst case, die. However, the mechanism underlying α-PVP-induced neurotoxicity is unknown. The objective of the present study was to investigate the effect of α-PVP on the central nervous system (CNS) and compare its neurotoxicity with that of methamphetamine (METH) in mice. Balb/c male mice (8 weeks old) were orally administered α-PVP (25 mg/kg) or METH (5 mg/kg). α-PVP induced a significant increase in locomotor activity, which occurred earlier than locomotor activity induced by METH. This increase was inhibited by the D1 receptor antagonist SCH23990 (50 µg/kg, i.p.) and the D2 receptor antagonist sulpiride (50 mg/kg, i.m.). The extracellular concentration of dopamine (DA) in the striatum, determined by in vivo microdialysis increased immediately after α-PVP administration. These results suggest that α-PVP stimulates DA release, causing an increase in locomotor activity, and that this stimulatory effect of α-PVP on CNS is mediated, at least in part, by the D1 and D2 receptors.
    No preview · Article · Jan 2014 · The Journal of Toxicological Sciences
    • "In addition to previously identified BZP and 3-TFMPP, three other controlled NPS were found amongst the new batch of products: a-pyrrolidinovalerophenone (a-PVP), naphyrone and a substituted methyl-cathinone with one of the MDAI products containing both the substituted methyl-cathinone and naphyrone. First, mass spectral data obtained concurred with published data for a-PVP [20] (Figure 2). Secondly, Brandt [8] previously reported that mass spectral data was not able to discriminate between a and b-naphyrone although the isomers could be separated on a 5% diphenyl/95% methyl siloxane GC column. "
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    ABSTRACT: The continuous appearance of novel psychoactive substances (NPS) in legal high products presents a challenge for the routine analytical laboratory. A rapid screening method for NPS analysis using fast gas chromatography mass spectrometry (fast GC-MS) is presented. Twenty-three analytes, including 5-iodo-2-aminoindane (5-IAI), 1-(thiophen-2-yl)-2-methylaminopropane (MPA), 1-benzylpiperazine (BZP), 4-methylmethcathinone (mephedrone), 5,6-methylenedioxy-2-aminoindane (MDAI) and methoxetamine (MXE) were separated within 4 min. The method was used to analyze 35 Internet and head shop purchased ‘legal high’ products with the successful identification of their active ingredients. As previously observed, legal high products do not always contain their stated ingredients. Of the group of products purchased as 5-IAI not one contained 5-IAI with several containing mixtures of substances either already controlled in the UK or under consideration by the Advisory Council on Misuse of Drugs (ACMD). The low bleed and high inertness of the chromatography column used ensured clean high quality mass spectrometry data which when combined with the short run time resulted in an efficient tool for NPS screening, even when standards were unavailable. Electron impact and chemical ionization mass spectra used in combination for the identification of unknown NPS are presented. Copyright
    No preview · Article · May 2013 · Drug Testing and Analysis
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    • "α-Pyrrolidinobutiophenone (α-PBP) Pyrrolidinyl H Methyl H No published data α-Pyrrolidinovalerophenone (α-PVP) Pyrrolidinyl H Ethyl H [45] 4-Methyl-α-Pyrrolidinobutiophenone (MPBP) Pyrrolidinyl 4-Methyl Methyl H [46] 4-Methyl-α-Pyrrolidino-α-methylpropiophenone Pyrrolidinyl 4-Methyl H Methyl [46] "
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    ABSTRACT: The purpose of this review is to evaluate what is currently known about the pharmacology of cathinone derivatives. Cathinone is the principal active constituent of khat responsible for the stimulant effects that have led khat to be known as a 'natural amphetamine'. Synthetic derivatives have been abused for their amphetamine-like stimulant effects, most notably methylone, methcathinone (ephedrone), and 4-methlymethcathinone (mephedrone). To date, cathinone and methcathinone have been studied most, demonstrating amphetamine-like effects in a range of in vitro and in vivo investigations, albeit less potently than amphetamines. In humans, cathinone derivatives are usually administered orally, and in some cases by insufflation. Methcathinone has a longer history of abuse, being produced from readily available starting materials, and administered by injection. Mephedrone has become the best publicised cathinone derivative, amid considerable media and public concern about its legal status, its ready availability, and reports of serious toxicity and deaths following its use. As a consequence, there has been a clampdown on cathinone derivatives, dramatically changing their legal status in a number of countries. However, little objective evidence-based comparative experiments have been conducted to date between these compounds and their related amphetamines in order to make clear risk judgements. Such assessments have largely been predictive in nature, based on their structural similarity to amphetamines. It can be assumed that, despite their illegal status, cathinone-related compounds will continue to be prevalent drugs of abuse for the foreseeable future.
    Full-text · Article · Jul 2011 · Drug Testing and Analysis
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