Pharmacodynamic Modeling for Change of Locomotor Activity by Methylphenidate in Rats

Purpose. The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed. Methods. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis. Results. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (K_i) of MPD for DA reuptake was estimated to be 41.3 ± 73.8 nM (mean ± SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of MPD could be represented by this model. Conclusions. The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by MPD, and may be useful for other DA reuptake inhibitors, such as amphetamine and methamphetamine.     

我院门诊病人处方中精神药品药物利用调查分析

目的 :了解我院精神药品 (psychotropicsubstances)使用情况 ,促进合理用药。方法 :采用限定日剂量和药物利用指数为指标对我院门诊精神药品的处方进行调查和分析。结果 ;平均药物利用指数在 1.0 0左右 ,用药时间大于 4wk的达 79.0 9% ,合并用药大于 2种药物的占 13.14 %。结论 :我院精神药品的使用基本合理 ,但用药时间较长 ,合并用药频度较高     

Workaholism is still a useful construct

Medical provision of orally-administered stimulants is a harm reduction technique that could reduce suffering and slow the spread of AIDS among cocaine misusers in Vancouver, B.C., Canada. However, experimentation with stimulant maintenance will be difficult to carry out until the public's exaggerated fears of cocaine and other stimulants, engendered by a prolonged “War on Drugs”, have subsided. This article explores the prospects for stimulant maintenance by (1) reviewing the actual dangers and benefits arising from use of cocaine and other stimulants, (2) describing small scale stimulant maintenance programs that already exist in various countries, and (3) drawing from Vancouver's experience with methadone maintenance to propose first steps towards stimulant maintenance. Although we focus our analysis on Vancouver, we believe it has wider applicability.     

Author Index to Abstracts

Abstract

Abuse of intravenous crushed Talwin (pentazocine) and Ritalin (methylphenidate) tablets has not been fully described. The objective of this study was to characterize intravenous pentazocine/methylphenidate abuse in emergency department patients and compare its clinical toxicity to pentazocine/tripelennamine. Cases of intravenous pentazocine/methylphenidate abuse presenting to the Truman Medical Center Emergency Department between August 1987 and November 1992 were identified. Information regarding patient demographics, drug abuse, chief complaints, evaluation, treatment, and disposition were obtained from the emergency department record. The clinical presentation was compared to 104 published cases of pentazocine/tripelennamine abuse. Twenty nine patients were treated 34 times. They were 32 ± 9 years of age, 48% male, and 52% black. Patients chief complaints were cardiovascular/pulmonary (N = 8), central nervous system (N = 7), localized infection (N = 7), gastrointestinal (N = 5), malaise (N = 5), trauma (N = 1), and gynecologic (N = 1). Treatment was primarily supportive and included supplemental oxygen and intravenous fluids. The clinical findings were similar to those reported for pentazocine/tripelennamine; 58% had the typical symptom complex of chest pain, anxiety, muscle spasm, dizziness, and nausea.     

A case of recurrent pneumothorax related to oral methylphenidate

Primary spontaneous pneumothorax (PSP) commonly occurs in young, tall, and thin males, without any identifiable cause except for emphysema-like changes (ELCs). However, other risk factors may be overlooked. Herein, we report the case of a 19-year-old male who presented with recurrent spontaneous pneumothorax while taking oral methylphenidate.     

Smart Drugs and Synthetic Androgens for Cognitive and Physical Enhancement: Revolving Doors of Cosmetic Neurology

Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. Currently, it represents one of the most debated topics in the neuroscience community. Human beings always wanted to use substances to improve their cognitive functions, from the use of hallucinogens in ancient civilizations in an attempt to allow them to better communicate with their gods, to the widespread use of caffeine under various forms (energy drinks, tablets, etc.), to the more recent development of drugs such as stimulants and glutamate activators. In the last ten years, increasing attention has been given to the use of cognitive enhancers, but up to now there is still only a limited amount of information concerning the use, effect and functioning of cognitive enhancement in daily life on healthy subjects. The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults. Moreover, the authors have explored the issue of cognitive enhancement compared to the use of Anabolic Androgenic Steroids (AAS) in sports. Finally, a brief overview of the ethical considerations surrounding human enhancement has been examined.     

The effect of methylphenidate on sustained attention among adolescents with attention-deficit hyperactivity disorder

Twenty-seven adolescents diagnosed as having attention-deficit hyperactivity disorder (ADHD) were tested twice with a computerized MATH-CPT (mathematics continuous performance test). In one administration, the participants took medication (methylphenidate, MPH) 1.5 hr before being tested. In another administration, the MATH-CPT was administered without the medication. Treatment with MPH improved the “overall attention level” and in measures of “reaction time” and “impulsivity.” MPH did not improve the performance in the four measures of sustained attention. Knowing that treatment with MPH does not improve sustained attention can be helpful in reaching a decision of whether or not a child should be treated with MPH.     

Twenty-four-week treatment with extended release methylphenidate improves emotional symptoms in adult ADHD

Abstract

Objectives. Treatment investigations with methylphenidate in adults with ADHD focus preferentially on the classical psychopathology: inattention, hyperactivity and impulsivity. ADHD-associated emotional symptoms, which are frequently present at least in ADHD subpopulations, were studied rarely. The vast majority of the placebo-controlled trials had observation periods between 4 and 8 weeks. To assess the medium- to long-term effects of extended release methylphenidate (MPH-ER) on emotional symptoms and other psychopathology frequently seen in ADHD patients, we conducted a large-scale, multicenter treatment study. Methods. We performed a randomised, 24-week, double-blind, placebo-controlled study in adults with ADHD. The diagnosis was made on the basis of the DSM-IV criteria, which were confirmed by clinical history and a structured psychopathological interview and the use of rating instruments. 363 patients were randomized to MPH-ER or placebo at a ratio of 2:1. The duration of the titration period was 5 weeks followed by a maintainance phase of 19 weeks. The efficacy measures were the observer rated 10-item Emotional Dysregulation Scale (EDS) derived from the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) and a self-report, six-item Emotional Lability Scale (ELS) extracted from the long version of the Conners Adult ADHD Self Report Scale (CAARS:S:L). In addition we used the SCL-90-R for the assessment of ADHD associated and comorbid psychopathology. Results. MPH-ER was statistically superior to placebo in reducing emotional symptoms as assessed by the EDS and the ELS. Obsessive-compulsive symptoms and those of problems with self-concept declined until the end of the observation period. The decline was more pronounced in MPH-ER treated individuals. The effects remained robust during the entire maintenance period until week 24. Symptoms of anxiety, depression, anger and hostility, phobia, paranoid ideations and psychoticism were not improved. Conclusions. MPH-ER appears to be an efficacious treatment for emotional symptoms with ADHD. Also obsessive-compulsive symptoms and problems with self-concept were affected positively.