- Rapid quantitative analysis of methylphenidate and ritalinic acid in oral fluid by liquid chromatography triple quadrupole mass spectrometry (LC-QqQ-MS). [Journal Article]
- JCJ Chromatogr B Analyt Technol Biomed Life Sci 2018 Jun 20; 1092:313-319
- Methylphenidate (MPH), which is metabolized into ritalinic acid (RA), is an amphetamine derivative largely used in the treatment of attention-deficit hyperactivity disorder, a neurological condition ...
Methylphenidate (MPH), which is metabolized into ritalinic acid (RA), is an amphetamine derivative largely used in the treatment of attention-deficit hyperactivity disorder, a neurological condition commonly diagnosed in early childhood. Ensuring that patients comply with clinical treatment is crucial and compliance is generally monitored in blood or urine specimens which, especially in the case of children, can be challenging to obtain on a repetitive basis. Here we report validation of a specific, non-invasive, and rapid dilute-and-shoot analytical method for the detection and quantitation of MPH and RA in oral fluid (OF). The method is based on liquid chromatography coupled to triple quadrupole MS with electrospray ionization utilizing dynamic MRM mode. Subject OF specimens were collected using a Quantisal™ device, processed, and diluted for analysis with seven-point quadratic calibration curves (weighting of 1/x) using MPH-d9 and (±)-threo-RA-d10 as internal standards. QC samples and diluted specimens showed intra- and inter-day bias and imprecision values no greater than ±12%. The LOD and LOQ for MPH were 0.1 and 0.5 ng/mL, respectively, and 0.2 ng/mL and 0.5 ng/mL for RA, respectively, indicating the validity of the method for identification and confirmation at low concentrations. Selectivity was specific for the analytes of interest and matrix effects were minimized through the use of internal standard based quantitation.
- Striatal Reinnervation Process after Acute Methamphetamine-Induced Dopaminergic Degeneration in Mice. [Journal Article]
- NRNeurotox Res 2018 Jun 22
- Methamphetamine (METH), an amphetamine derivate, may increase the risk of developing Parkinson's disease (PD). Human and animal studies have shown that METH produces persistent dopaminergic neurotoxi...
Methamphetamine (METH), an amphetamine derivate, may increase the risk of developing Parkinson's disease (PD). Human and animal studies have shown that METH produces persistent dopaminergic neurotoxicity in the nigrostriatal pathway, despite initial partial recovery. To determine the processes leading to early compensation, we studied the detailed morphology and distribution of tyrosine hydroxylase immunoreactive fibers (TH-ir) classified by their thickness (types I-IV) before and after METH. Applying three established neurotoxic regimens of METH: single high dose (1 × 30 mg/kg), multiple lower doses (3 × 5 mg/kg) or (3 × 10 mg/kg), we show that METH primarily damages type I fibers (the thinner ones), and to a much lesser extend types II-IV fibers including sterile axons. The striatal TH terminal partial recovery process, consisting of a progressive regrowth increases in types II, III, and IV fibers, demonstrated by co-localization of GAP-43, a sprouting marker, was observed 3 days post-METH treatment. In addition, we demonstrate the presence of growth-cone-like TH-ir structures, indicative of new terminal generation as well as improvement in motor functions after 3 days. A temporal relationship was observed between decreases in TH-expression and increases in silver staining, a marker of degeneration. Striatal regeneration was associated with an increase in astroglia and decrease in microglia expression, suggesting a possible role for the neuroimmune system in regenerative processes. Identification of regenerative compensatory mechanisms in response to neurotoxic agents could point to novel mechanisms in countering the neurotoxicity and/or enhancing the regenerative processes.
- Roadside survey of alcohol and drug use among Norwegian drivers in 2016-17: a follow up of the 2008-9 survey. [Journal Article]
- TITraffic Inj Prev 2018 Jun 21; :1-32
- CONCLUSIONS: The proportion of samples that tested positive for alcohol had not changed since 2008-9, whereas the proportions that tested positive for benzodiazepines and amphetamines were lower. There are several possible reasons for the reduction: implementation of legal limits for 28 drugs in 2012-16, increased use of drug recognition tests, the implementation of drug screening instruments and automatic number plate recognition by the police since 2010, more focused enforcement of the DUI law, better information to drivers, and changes in drug prescriptions.
- Decision-Making Under Risk, but Not Under Ambiguity, Predicts Pathological Gambling in Discrete Types of Abstinent Substance Users. [Journal Article]
- FPFront Psychiatry 2018; 9:239
- This study explored how different forms of reward-based decision-making are associated with pathological gambling (PG) among abstinent individuals with prior dependence on different classes of drugs....
This study explored how different forms of reward-based decision-making are associated with pathological gambling (PG) among abstinent individuals with prior dependence on different classes of drugs. Participants had lifetime histories of either "pure" heroin dependence (n = 64), "pure" amphetamine dependence (n = 51), or polysubstance dependence (n = 89), or had no history of substance dependence (n = 133). Decision-making was assessed via two neurocognitive tasks: (1) the Iowa Gambling Task (IGT), a measure of decision-making under ambiguity (i.e., uncertain risk contingencies); and (2) the Cambridge Gambling task (CGT), a measure of decision-making under risk (i.e., explicit risk contingencies). The main effects of neurocognitive performance and drug class on PG (defined as ≥3 DSM-IV PG symptoms) as well as their interactional effects were assessed via multiple linear regression. Two CGT indices of decision-making under risk demonstrated positive main effects on PG. Interaction effects indicated that the effects of decision-making under risk on PG were largely consistent across participant groups. Notably, a linear relationship between greater CGT Risk-Taking and PG symptoms was not observed among amphetamine users, whereas IGT performance was selectively and positively associated with PG in polysubstance users. Overall, results indicate that reward-based decision-making under risk may represent a risk factor for PG across substance users, with some variations in these relationships influenced by specific class of substance of abuse.
- Magnesium in the Central Nervous System [BOOK]
- BOOKUniversity of Adelaide Press: Adelaide (AU)
- Addiction to different substances is considered to be a psychiatric disorder. Magnesium reduces the intensity of addiction to opiates and psychostimulants (cocaine, amphetamine, nicotine, and others)...
Addiction to different substances is considered to be a psychiatric disorder. Magnesium reduces the intensity of addiction to opiates and psychostimulants (cocaine, amphetamine, nicotine, and others). It also decreases the auto-administration of cocaine and the relapse into cocaine and amphetamine intake, as well as reducing the experimental addiction to morphine, cocaine and other substances in animals. In heroin addicts, alcohol consumers and other drug abusers, the plasma and intracellular magnesium concentration is lower compared to healthy subjects. We consider that one of the mechanisms by which magnesium reduces the consumption of some highly addictive substances is its moderate effect of stimulating the reward system. However, other main mechanisms involved in magnesium’s action are the reduction of dopamine and glutamate release at presynaptic terminals in the brain, the decrease of NO synthase activity, the stimulation of GABAergic system activity, the reduction of postsynaptic NMDA receptor activity, and the reduction of some neuromediators released by Ca2+ and acting at calcium channels. Apart from the action of magnesium ions during emerging addiction, administration of this cation after the appearance of withdrawal syndrome reduces the intensity of the clinical symptoms. There are data that show that stress increases the vulnerability of people to develop addiction to different substances, and also reduces drug-free time and increases the incidence of relapse in heroin addicts. Stress increases catecholamine release and stimulates magnesium release from the body. This decrease in magnesium concentration is one of the important factors that hastens relapse.
- Enantiomeric separation of Novel Psychoactive Substances by capillary electrophoresis using (+)-18-crown-6-tetracarboxylic acid as chiral selector. [Journal Article]
- CChirality 2018 Jun 19
- In the recent years, hundreds of Novel Psychoactive Substances (NPS) have entered both the European and the global drug market. These drugs, which are mainly used for recreational matters, have cause...
In the recent years, hundreds of Novel Psychoactive Substances (NPS) have entered both the European and the global drug market. These drugs, which are mainly used for recreational matters, have caused serious social problems. Every year, the spectrum of these misused drugs is enlarged by new derivatives, which are produced by modifications of basic structures of already well-known substances. Additionally, a lot of them possess a stereogenic center which leads to 2 enantiomeric forms. The fact that the pharmacological effects and potencies of the enantiomers of these chiral NPS may differ can be assumed from a broad spectrum of active pharmaceutical ingredients. For this reason, analytical method development regarding enantiomeric separation for these classes of substances is of great pharmaceutical and medical interest. The aim of this work was to create an easy-to-prepare chiral capillary electrophoresis method for the enantioseparation of NPS which contains a primary amino group by means of (+)-18-crown-6-tetracarboxylic acid as chiral selector. Novel Psychoactive Substances were purchased at various Internet stores or represent samples seized by Austrian police. The effects of selector concentration, the electrolyte composition, and the addition of organic modifiers to the background electrolyte on enantioseparation were investigated. Under optimized conditions, the use of 20-mM (+)-18-crown-6-tetracarboxylic acid, 10-mM Tris, and 30-mM citric acid buffer at pH 2.10 turned out to be effective. Fifteen of 24 tested NPS were resolved in their enantiomers within 15 minutes. It was found that all NPS were traded as racemic mixtures.
- Prevalence of drug use among drivers based on mandatory, random tests in a roadside survey. [Journal Article]
- PlosPLoS One 2018; 13(6):e0199302
- CONCLUSIONS: Different patterns of use are detected depending on the drug considered. Preventive drug tests should not only be conducted on weekends and at night-time, and need to be reinforced for drivers of commercial vehicles. Active educational campaigns should focus on the youngest age-group of male drivers.
- Disposition of Methamphetamine and Major Metabolites in Mice: Role of Organic Cation Transporter 3 (Oct3) in Tissue Selective Accumulation of para-hydroxymethamphetamine. [Journal Article]
- DMDrug Metab Dispos 2018 Jun 18
- Methamphetamine is one of the most widely abused illicit drugs. While human intoxication and multiple tissue toxicities frequently occur in abusers, little is known about the distribution of methamph...
Methamphetamine is one of the most widely abused illicit drugs. While human intoxication and multiple tissue toxicities frequently occur in abusers, little is known about the distribution of methamphetamine or its primary metabolites, amphetamine and para-hydroxymethamphetamine (p-OHMA), to their sites of toxicity. This study determined the pharmacokinetics, tissue exposure, and partition ratios of methamphetamine and major metabolites in various mouse tissues and investigated the impact of organic cation transporter 3 (Oct3) following intravenous injection of methamphetamine to male Oct3+/+ and Oct3-/- mice. Methamphetamine, amphetamine and p-OHMA were readily detectable in plasma with Oct3+/+ and Oct3-/- mice displaying similar plasma pharmacokinetic profiles for all three analytes. In addition to kidney and liver, salivary glands highly accumulated methamphetamine, amphetamine and p-OHMA with total exposure 3.3 to 9.4-fold higher than plasma AUC. Consistent with being an Oct3 substrate, p-OHMA AUC in salivary glands is reduced by 50% in Oct3-/- mice. p-OHMA AUC in skeletal muscle is also significantly reduced in Oct3-/- mice. Our data identified salivary glands as a novel site of high accumulation of methamphetamine and metabolites, which may underlie methamphetamine toxicity in this tissue. Furthermore, our study identified Oct3 as an important determinant of tissue uptake and exposure to p-OHMA in salivary glands and skeletal muscle. Our findings suggest that local tissue accumulation of methamphetamine and/or its metabolites may play a role in several of the reported peripheral toxicities of methamphetamine and Oct3 can significantly impact tissue exposure to its substrates without affecting systemic elimination.
- A new amphetamine oral suspension (Adzenys ER) for ADHD. [Journal Article]
- MLMed Lett Drugs Ther 2018 Jun 18; 60(1549):e106-e108
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- Detection and identification of designer drugs by nanoparticle-based NMR chemosensing. [Journal Article]
- CSChem Sci 2018 Jun 07; 9(21):4777-4784
- Properly designed monolayer-protected nanoparticles (2 nm core diameter) can be used as nanoreceptors for selective detection and identification of phenethylamine derivatives (designer drugs) in wate...
Properly designed monolayer-protected nanoparticles (2 nm core diameter) can be used as nanoreceptors for selective detection and identification of phenethylamine derivatives (designer drugs) in water. The molecular recognition mechanism is driven by the combination of electrostatic and hydrophobic interactions within the coating monolayer. Each nanoparticle can bind up to 30-40 analyte molecules. The affinity constants range from 105 to 106 M-1 and are modulated by the hydrophobicity of the aromatic moiety in the substrate. Detection of drug candidates (such as amphetamines and methamphetamines) is performed by using magnetization (NOE) or saturation (STD) transfer NMR experiments. In this way, the NMR spectrum of the drug is isolated from that of the mixture, allowing broad-class multianalyte detection and even identification of unknowns. The introduction of a dimethylsilane moiety in the coating monolayer allows performing STD experiments in complex mixtures. In this way, a detection limit of 30 μM is reached with standard instruments.