Dose–response effects of methylphenidate on ecologically valid measures of academic performance and classroom behavior in adolescents with ADHD.

The effects of methylphenidate on the academic performance and classroom behavior of 45 adolescents with attention deficit disorder with hyperactivity were studied. During a 6-week, placebo-controlled medication assessment in the context of a summer treatment program, participants received a double-blind, crossover trial of 3 doses of methylphenidate. Dependent measures included note-taking quality, quiz and worksheet scores, written language usage and productivity, teacher ratings, on-task and disruptive behavior, and homework completion. Group data showed positive effects of methylphenidate on academic measures; however, the greatest benefit came with the lowest dose. Although additional benefit did occur for some participants with higher doses, the largest increment of change usually occurred between the placebo and 10-mg dose. Many adolescents did not experience added benefit with increased dosages, and in some cases they experienced deterioration. Guidelines for assessment of medication effects are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluating elevated release liner adhesion of a transdermal drug delivery system (TDDS): A study of Daytrana™ methylphenidate transdermal system

Background: Complaints from healthcare providers that the adhesive on the Daytrana? methylphenidate transdermal drug delivery system (TDDS) adhered to the release liner to such an extent that the release liner could not be removed prompted this study. Daytrana? has a packaging system consisting of a moisture-permeable pouch contained within a sealed tray containing a desiccant; the tray is impermeable to ambient moisture. The objective of this project was to determine if the Daytrana? packaging system influenced the difficulty in removing the release liner.

Method: Both a sealed tray and an open tray containing sealed pouches were placed into an environmental chamber at 25°C and 60% relative humidity for 30 days; afterwards, release liner removal testing using a peel angle of 90° and a peel speed of 300?mm/min was performed.

Results: TDDS from open chamber trays required less force to remove the release liner than did TDDS from closed chamber trays. For the 10?mg/9?h TDDS and the 15?mg/9?h TDDS (the dosages examined), there were substantial differences in release liner removal force between an old lot and a new lot for closed chamber trays but not for open chamber trays.

Conclusion: The results demonstrate that for this particular TDDS, storage conditions such as humidity influence release liner adhesion. This project also demonstrates that, to ensure adequate product quality, adhesion needs to become an important design parameter, and the design of a TDDS should consider the ability to remove the release liner under anticipated storage conditions.     

液相色谱-串联质谱法确证人尿中的利他林及其主要代谢物

建立了固相萃取-液相色谱-串联质谱法同时确证人尿中的利他林及其主要代谢物利他林酸的方法。尿样中的药物经反相C₁₈固相萃取柱净化、氮气吹至干,以甲睾为内标,用流动相溶解后进行液相色谱-串联质谱法测定。该方法的最低检出限为5 μg•L^-1;利他林和利他林酸的回收率分别为80.6%和68.4%;批内和批间的相对标准偏差小于6.0%,能满足国际反兴奋剂机构(WADA)对其最低检测能力500 μg•L^-1的要求。     

The effects of methylphenidate in the classroom: What dosage, for which children, for what problems?

In this study the authors conducted single-case analyses of the dosage and time-course effects of methylphenidate (MPH; Ritalin) on disruptive classroom behavior, math and reading performance, and social engagement. Clear individual differences were demonstrated (a) across children (aged 7 yrs) with attention deficit hyperactivity disorder (ADHD); (b) across academic, behavioral, and social domains of functioning; (c) for dose-response effects; and (d) in the onset and duration of effects. These results are in contrast to the majority of group studies that suggest a generally positive and linear dose-response effect for MPH across both children and domains of functioning. No particular dose-response relationship between disruptive behavior and academic performance was indicated. However, an increasing dosage of MPH was associated with increasing social withdrawal for 2 of the 3 participants. Implications for school-based medication evaluations and for designing optimal comprehensive interventions for children who receive MPH are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Advancing the spontaneous hypertensive rat model of attention deficit/hyperactivity disorder.

To advance the spontaneous hypertensive rat (SHR) model of attention deficit/hyperactivity disorder (ADHD), experiments examined the SHR in tasks recognized to assess functioning of the prefrontal cortex or dorsal striatal. Tasks included odor-delayed win-shift (nonspatial working and reference memory), win-stay (habit learning), and attentional set-shifting (attention and behavioral flexibility). In Experiment 1, the SHR strain was compared with Wistar-Kyoto (WKY) and Wistar-Kyoto Hypertensive (WKHT) strains on the first 2 tasks. In Experiment 2, oral methylphenidate (1.5 mg/kg) and vehicle (water) were evaluated on all 3 tasks in SHR and WKY strains. Results demonstrated that the SHR made significantly more errors in the odor-delayed win-shift, win-stay, and attentional set-shifting tasks compared with the WKY. Similar performances in the WKY and WKHT indicated that deficits observed in the SHR were not related solely to hypertension. Treating the SHR with methylphenidate eliminated strain differences in all 3 tasks. These findings provide evidence that the SHR is a valid model for studying ADHD-associated neurocognitive deficits. Moreover, the current behavioral approach is appropriate to assess novel medications developed to target ADHD-associated neurocognitive deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence.

In this 12-week double-blind placebo-controlled trial of methylphenidate (MTP) versus placebo in 48 cocaine-dependent attention-deficit/hyperactivity disorder (ADHD) adults, the authors sought to determine whether MTP would be safe, control ADHD symptoms, and affect cocaine use. Efficacy indexes revealed significantly greater ADHD symptom relief in the MTP group. There were no group differences in self-reported cocaine use, urinalysis results, or cocaine craving. Because of the relatively small sample size, the results are preliminary. However, the authors found that MTP improved subjective reports of ADHD symptoms and did not worsen cocaine use while participants were in treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats

Methylphenidate (MPH) is among the main drugs prescribed to treat patients with attention-deficit and hyperactivity disease (ADHD). MPH blocks both the norepinephrine and dopamine reuptake transporters (NET and DAT, respectively). Our study was aimed at further understanding the mechanisms by which MPH could modulate neurotransmitter efflux, using ex vivo radiolabelled neurotransmitter assays isolated from rats. Here, we observed significant dopamine and norepinephrine efflux from the prefrontal cortex (PFC) after MPH (100 µM) exposure. Efflux was mediated by both dopamine and norepinephrine terminals. In the striatum, MPH (100 µM) triggered dopamine efflux through both sodium- and vesicular-dependent mechanisms. Chronic MPH exposure (4 mg/kg/day/animal, voluntary oral intake) for 15 days, followed by a 28-day washout period, increased the firing rate of PFC pyramidal neurons, assessed by in vivo extracellular single-cell electrophysiological recordings, without altering the responses to locally applied NMDA, via micro-iontophoresis. Furthermore, chronic MPH treatment resulted in decreased efficiency of extracellular dopamine to modulate NMDA-induced firing activities of medium spiny neurons in the striatum, together with lower MPH-induced (100 µM) dopamine outflow, suggesting desensitization to both dopamine and MPH in striatal regions. These results indicate that MPH can modulate neurotransmitter efflux in brain regions enriched with dopamine and/or norepinephrine terminals. Further, long-lasting alterations of striatal and prefrontal neurotransmission were observed, even after extensive washout periods. Further studies will be needed to understand the clinical implications of these findings.     

手性转换成功与失败的启示

右美沙芬、沙利度胺和哌克昔林等药害事件再次揭示药物作用的立体选择性的重要性 ,艾美拉唑和依酞普兰是手性转换成功的范例 ,而 (R) 氟西汀因判断失误造成了手性转换的流产 ,因成功的手性转换带来灾难性后果的是右芬氟拉明 ,左西替利嗪和依匹克隆则通过手性转换延长了生命周期。     

Methylphenidate Restores Behavioral and Neuroplasticity Impairments in the Prenatal Nicotine Exposure Mouse Model of ADHD: Evidence for Involvement of AMPA Receptor Subunit Composition and Synaptic Spine Morphology in the Hippocampus

In ADHD treatment, methylphenidate (MPH) is the most frequently used medication. The present work provides evidence that MPH restored behavioral impairments and neuroplasticity due to changes in AMPAR subunit composition and distribution, as well as maturation of dendritic spines, in a prenatal nicotine exposure (PNE) ADHD mouse model. PNE animals and controls were given a single oral dose of MPH (1 mg/kg), and their behavior was tested for attention, hyperactivity, and working memory. Long-term potentiation (LTP) was induced and analyzed at the CA3/CA1 synapse in hippocampal slices taken from the same animals tested behaviorally, measuring fEPSPs and whole-cell patch-clamp EPSCs. By applying crosslinking and Western blots, we estimated the LTP effects on AMPAR subunit composition and distribution. The density and types of dendritic spines were quantified by using the Golgi staining method. MPH completely restored the behavioral impairments of PNE mice. Reduced LTP and AMPA-receptor-mediated EPSCs were also restored. EPSC amplitudes were tightly correlated with numbers of GluA1/GluA1 AMPA receptors at the cell surface. Finally, we found a lower density of dendritic spines in hippocampal pyramidal neurons in PNE mice, with a higher fraction of thin-type immature spines and a lower fraction of mushroom mature spines; the latter effect was also reversed by MPH.     

Construct validity of an attention rating scale for traumatic brain injury.

Attention deficits are nearly ubiquitous after traumatic brain injury (TBI). In the subacute phase of moderate to severe TBI, these deficits may be difficult to measure with the precision needed to predict outcomes, assess degree of recovery, and monitor treatment response. This article reports the findings of four studies, three observational and one a randomized, controlled treatment trial of methylphenidate (MP), designed to provide construct validation of the Moss Attention Rating Scale (MARS), an observational measure of attention dysfunction following TBI. One hundred seven participants with moderate to severe TBI were enrolled during treatment on an inpatient rehabilitation unit. MARS scores were provided independently by four rehabilitation disciplines (Physical, Occupational and Speech Therapies and Nursing). Results indicated that the MARS: (1) is more strongly related to concurrent measures of cognitive versus physical disability, supporting its validity as a measure of cognition, (2) is more strongly related to concurrent psychometric measures of attention versus measures thought to rely less on attention, supporting its validity as a measure of attention; and (3) predicts 1-year outcomes of TBI better than psychometric measures of attention. However, the MARS (4) was not differentially affected by MP versus placebo treatment. Results support the construct validity and utility of the MARS, with further research needed to clarify its role in treatment outcome assessment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)