Psychostimulant Drugs (psychostimulant + drug)

Distribution by Scientific Domains


Selected Abstracts


Neurotransmitter transporters and their impact on the development of psychopharmacology

BRITISH JOURNAL OF PHARMACOLOGY, Issue S1 2006
Leslie Iversen
The synaptic actions of most neurotransmitters are inactivated by reuptake into the nerve terminals from which they are released, or by uptake into adjacent cells. A family of more than 20 transporter proteins is involved. In addition to the plasma membrane transporters, vesicular transporters in the membranes of neurotransmitter storage vesicles are responsible for maintaining vesicle stores and facilitating exocytotic neurotransmitter release. The cell membrane monoamine transporters are important targets for CNS drugs. The transporters for noradrenaline and serotonin are key targets for antidepressant drugs. Both noradrenaline-selective and serotonin-selective reuptake inhibitors are effective against major depression and a range of other psychiatric illnesses. As the newer drugs are safer in overdose than the first-generation tricyclic antidepressants, their use has greatly expanded. The dopamine transporter (DAT) is a key target for amphetamine and methylphenidate, used in the treatment of attention deficit hyperactivity disorder. Psychostimulant drugs of abuse (amphetamines and cocaine) also target DAT. The amino-acid neurotransmitters are inactivated by other families of neurotransmitter transporters, mainly located on astrocytes and other non-neural cells. Although there are many different transporters involved (four for GABA; two for glycine/D -serine; five for L -glutamate), pharmacology is less well developed in this area. So far, only one new amino-acid transporter-related drug has become available: the GABA uptake inhibitor tiagabine as a novel antiepileptic agent. British Journal of Pharmacology (2006) 147, S82,S88. doi:10.1038/sj.bjp.0706428 [source]


The protective effect of melatonin on methamphetamine-induced calpain-dependent death pathway in human neuroblastoma SH-SY5Y cultured cells

JOURNAL OF PINEAL RESEARCH, Issue 2 2010
Wilasinee Suwanjang
Abstract:, Methamphetamine (METH) is a potent psychostimulant drug that may cause neuronal cell degeneration. The underlying mechanisms of METH-induced neuronal toxicity remains poorly understood. In this study, we investigated an important role of calpain-dependent cascades in methamphetamine-induced toxicity in human dopaminergic neuroblastoma SH-SY5Y cultured cell lines. In addition, the protective effect of melatonin against METH-induced calpain-dependent death pathway was also investigated. The results of this study show that METH significantly decreased cell viability and tyrosine hydroxylase phosphorylation in SH-SY5Y cultured cells. Melatonin reversed the toxic effect of METH by inducing cell viability. In addition, melatonin was able to restore the reduction in mitochondrial function and phosphorylation of tyrosine hydroxylase in SH-SY5Y treated cells. An induction of calpain expression and activity but a reduction of calpain inhibitor (calpastatin) protein levels were observed in SH-SY5Y cells treated with METH but these effects were diminished by melatonin. These results implicated calpain-dependent death pathways in the processes of METH-induced toxicity and also indicated that melatonin has the capacity to reverse this toxic effect in SH-SY5Y cultured cells. [source]


Acute neuropsychological effects of methylphenidate in stimulant drug-naïve boys with ADHD II , broader executive and non-executive domains

THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 11 2006
Sinéad M. Rhodes
Background:, Accumulating evidence supports methylphenidate-induced enhancement of neuropsychological functioning in attention deficit hyperactivity disorder (ADHD). The present study was designed to investigate the acute effects of the psychostimulant drug, methylphenidate (MPH), on neuropsychological performance in stimulant naïve boys with ADHD. Methods:, Seventy-three drug-naïve boys (age 7,15) with ADHD (combined type) completed neuropsychological tasks from the CANTAB battery under randomised, placebo controlled, double-blind conditions following an acute challenge with either placebo (n = 24), .3 (n = 25) or .6 (n = 24) mg/kg oral MPH. Results:, MPH did not impair performance on any task. MPH (.6 mg/kg) lengthened response latencies on a task of Spatial Recognition, shortened response times on a Reaction Time task and restored performance on a Delayed Matching to Sample visual, non-working memory task. Contrary to predictions, MPH did not enhance performance on tasks with a prominent executive component, including Go/NoGo, Spatial Working Memory, Stockings of Cambridge and Attentional Set shifting tasks. Conclusions:, Acute administration of MPH to drug-naïve boys with ADHD did not impair neuropsychological performance. Acute MPH enhanced performance on some aspects of non-executive functioning. MPH-induced slowing of responding on a relatively complex Spatial Recognition memory task and quickened responding on a reaction time task requiring less cognitive resources suggests that MPH may act by improving self-regulatory ability. MPH may not exert its effects on neuropsychological functioning by enhancing executive processes. [source]


Do the old psychostimulant drugs have a role in managing treatment-resistant depression?

ACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2010
G. Parker
Parker G, Brotchie H. Do the old psychostimulant drugs have a role in managing treatment-resistant depression? Objective:, As the authors have observed clinical benefit from the psychostimulants methylphenidate and dexamphetamine for treating resistant melancholic and bipolar depression, those drugs were evaluated in a consecutively recruited sample of 50 such patients. Method:, Patients (27 bipolar, 23 unipolar) received either methylphenidate (n = 44) or dexamphetamine (n = 6), with 30 having it prescribed as an augmenting drug and 20 as monotherapy. At the final review, ranging from 6 weeks to 62 months (mean 57 weeks), 52% were still receiving their psychostimulant. Results:, Thirty-four per cent reported the psychostimulant as distinctly improving their depression, 30% reported some level of improvement and 36% reported no improvement and/or side-effects. For improvers, the modal dose of methylphenidate was 20 mg. Significant side-effects were reported by 18% (including one manic response), switching was rare and limited to the bipolar subjects, and most side-effects were minor. Any positive response occurred rapidly and loss of efficacy was rare. Testing of tricyclic levels in some patients suggested that stimulant drugs may raise tricyclic levels in those who are rapid metabolizers. Conclusion:, Although this study was not controlled, the high success rate in a diagnostically refined sample implies that the psychostimulants may be efficacious for patients with melancholic and bipolar depression who have failed to respond to orthodox antidepressant drugs. [source]


PRECLINICAL STUDY: Morphine withdrawal decreases responding reinforced by sucrose self-administration in progressive ratio

ADDICTION BIOLOGY, Issue 2 2007
Dengke Zhang
ABSTRACT Previous studies have shown that withdrawal from psychostimulant drugs such as d -amphetamine or methamphetamine decreases motivation to work for a natural reinforcement, which is thought to be associated with the withdrawal-induced depressive state and hypofunction of the mesolimbic dopamine system. However, to our knowledge, studies exploring the effect of morphine withdrawal on motivation for a natural reinforcement are lacking. The purpose of the present study was to examine whether motivation to work for a natural reinforcement changes during morphine withdrawal. Three groups of male Sprague,Dawley rats were trained to respond on a nose poke for a 4% sucrose solution under a progressive ratio schedule and were subsequently administered a 10-day regimen of injection of high or low dose of morphine or saline. Their duration of break point and withdrawal symptoms were assessed. The finding showed that break points were significantly reduced on day 1 and persisted to at least day 10 of withdrawal without change in locomotor activity. There were hardly any differences bear mentioning when comparing the magnitude of the decrease between the high- and the low-dose group, whereas the withdrawal scales were significant greater in the high-dose group than in the low-dose group. The results suggest that the morphine withdrawal resulted in decreased motivation to obtain the natural reinforcement. The progressive ratio procedure may be a useful technique for evaluation of changes in motivation for natural reinforcing stimuli following withdrawal from opiates. [source]