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.

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    • "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.
    The Journal of Toxicological Sciences 01/2014; 39(1):1-6. DOI:10.2131/jts.39.1 · 1.29 Impact Factor
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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.
    Drug Testing and Analysis 07/2011; 3(7-8):439-53. DOI:10.1002/dta.313 · 2.51 Impact Factor
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    • "Very recently, Ojanperä et al. published their results about MDPV findings from the urine of opioid-dependent patients [5], which is, other than our results, the only published study about MDPV in clinical samples. There are, however, some data on the pharmacology and toxicology of other structurally similar designer drugs of pyrrolidinophenone or cathinone types available [6] [7] [8] [9]. "
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    ABSTRACT: Starting in 2008 a new designer drug, 3,4-methylenedioxypyrovalerone (MDPV) appeared among users of illegal drugs in Finland. Since then there have been several seizures of MDPV by police and customs and it has been connected to many crimes of different types. In this study the incidence and impact of the use of MDPV in drivers suspected of being under the influence of drugs (DUID) in Finland was assessed. Since autumn 2009, blood samples from drivers suspected of DUID in Finland have been analysed for the presence of MDPV. A new LC-MS/MS method for the determination of MDPV in serum was established. In order to assess the impact of MDPV on driving performance, drug and alcohol findings of positive MDPV cases were compared with data from the clinical examination carried out while the suspect was under arrest. In a period of one year there were 259 positive MDPV cases from apprehended drivers (5.7% of all confirmed DUID cases). In 80% of the cases in which MDPV was found, amphetamine was also present. Benzodiazepines were also frequently found together with MDPV, which was to be expected since in Finland, in our experience, stimulants are very often used together with benzodiazepines. In most cases it remained unclear whether the observed psycho-physical achievement deficiency was induced by MDPV because the concentrations of other drugs, especially other stimulants, were often high. However, in some subjects, MDPV, or MDPV in combination with other substances was the most probable cause of the impairment. The concentrations of MDPV varied from 0.016mg/L to over 8.000mg/L. Little is known about the pharmacology of MDPV. However, based on our findings it is clear that MDPV has a serious impact on traffic safety in Finland.
    Forensic science international 04/2011; 210(1-3):195-200. DOI:10.1016/j.forsciint.2011.03.015 · 2.14 Impact Factor
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