Background And Purpose: New psychoactive substances such as N-ethylpentylone (NEP) are continuously emerging in the illicit drug market, and knowledge of their effects and risks, which may vary between sexes, is scarce. Our present study compares some key effects of NEP in male and female mice.
Experimental Approach: Psychostimulant, rewarding and reinforcing effects were investigated by tracking locomotor activity, conditioned place preference (CPP) paradigm and through a self-administration (SA) procedure, respectively, in CD1 mice.
The utility of classical drugs used to treat psychiatric disorders (e.g., antidepressants, anxiolytics) is often limited by issues of lack of efficacy, delayed onset of action or side effects.
View Article and Find Full Text PDFTriamcinolone hexacetonide (THA) is a synthetic glucocorticoid (GC) used by intra-articular (IA) administration. GCs are prohibited in sports competitions by systemic routes, and they are allowed by other routes considered of local action (IA administration, among others). The aim of the present work was to study the metabolic profile of THA in urine and plasma following IA administration.
View Article and Find Full Text PDFMephedrone (MEPH), the most widely consumed synthetic cathinone, has been associated with acute toxicity episodes. The aim of this report was to study its metabolic disposition and the impact of genetic variation of CYP2D6 on MEPH metabolism, in a dose range compatible with its recreational use. A randomized, crossover, phase I clinical trial was performed.
View Article and Find Full Text PDFBackground: The unprecedented proliferation of new psychoactive substances (NPS) threatens public health and challenges drug policy. Information on NPS pharmacology and toxicity is, in most cases, unavailable or very limited and, given the large number of new compounds released on the market each year, their timely evaluation by current standards is certainly challenging.
Aims: We present here a metabolomics-targeted approach to predict the pharmacological profile of NPS.
Purpose: The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function).
Materials And Methods: In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study.
3,4-methylenedioxypyrovalerone or MDPV is a synthetic cathinone with psychostimulant properties more potent than cocaine. We quantified this drug in the striatum after subcutaneous administration to rats. MDPV reached the brain around 5 min after its administration and peaked at 20-25 min later.
View Article and Find Full Text PDFProg Neuropsychopharmacol Biol Psychiatry
August 2013
Introduction: Methylone (3,4-methylenedioxymethcathinone) is a new psychoactive substance and an active ingredient of "legal highs" or "bath salts". We studied the pharmacokinetics and locomotor activity of methylone in rats at doses equivalent to those used in humans.
Material And Methods: Methylone was administered to male Sprague-Dawley rats intravenously (10mg/kg) and orally (15 and 30 mg/kg).
Unlabelled: The synthetic psychostimulant MDMA (± 3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT).
View Article and Find Full Text PDF3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 in a previous study, the aim of this work was to study in humans the activity of CYP1A2 in vivo after CYP2D6 had been inhibited by MDMA, using caffeine as a probe drug.
View Article and Find Full Text PDFBackground And Objective: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6 and is also a potent mechanism-based inhibitor of the enzyme. This study assessed the inhibition and recovery half-life of CYP2D6 and CYP3A4 activity in female subjects by administering the probe drug dextromethorphan before and repeatedly after MDMA administration.
View Article and Find Full Text PDFBackground: Rupatadine is an oral active antihistamine and platelet-activating factor antagonist indicated for the management of allergic rhinitis and chronic urticaria in Europe.
Objective: The purpose of this study was to describe the effect of the concomitant administration of azithromycin and rupatadine on the pharmacokinetics of rupatadine and its metabolites after repeated doses.
Methods: This was a multiple-dose, randomized, open-label, 2-way, crossover, Phase I study in which healthy male and female volunteers received rupatadine 10 mg once a day for 6 days either alone or with azithromycin 500 mg on day 2 and 250 mg from day 3 to day 6.
Eur J Drug Metab Pharmacokinet
October 2008
Rupatadine is a new oral antihistaminic agent used for the management of allergic inflammatory conditions, such as rhinitis and chronic urticaria. The aim of the present study was to develop a population pharmacokinetic/pharmacodynamic (PKPD) model for the description of the effect of rupatadine and one of its active metabolites, desloratadine, on the histamine-induced flare reaction and to predict the response to treatment after repeated administrations of rupatadine. Both rupatadine and desloratadine were characterized by two-compartmental kinetics.
View Article and Find Full Text PDFBackground: Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries.
Objective: The purpose of this study was to describe the effect of the concomitant intake of food on the pharmacokinetic profile and bioavailability of a single dose of rupatadine.