Abstract:
:Oxidant stress resulting from excess dopamine (DA) may contribute to the development and progression of Parkinson's disease (PD). Free radicals resulting from the enzymatic metabolism of DA are most often discussed in this regard. However, levodopa (L-DOPA) and DA can also undergo autooxidation, producing free radicals as well as cytotoxic metabolites. We evaluated the neurotoxic effects of the two stereoisomers of L-DOPA to differentiate between enzyme-mediated and autooxidation mechanisms. Various concentrations of D- or L-DOPA (1 mM through 10 nM) were added to freshly harvested rostral mesencephalic tegmentum cultures. After 72 h, the cultures were fixed and stained for tyrosine hydroxylase (TH). The number of TH-immunoreactive (THir) neurons was then assessed and used as an index of DA neuron survival. Both D- and L-DOPA induced a dose-dependent loss of THir neurons (F10,21 = 135.75, p < 0.0001 and F10,21 = 142.53, p < 0.0001, respectively) with ED50 values of 10(-5.3) and 10(-5.2) M, respectively. The dose-response curves for each drug were not significantly different from one another (F1,43 = 0.09, p > 0.05). Moreover, both drugs killed THir as well as non-THir cells at high concentrations, suggesting a nonspecific toxic effect. These data are most consistent with an enzyme-independent, autooxidation-mediated mechanism for DA neuron loss.
journal_name
Clin Neuropharmacoljournal_title
Clinical neuropharmacologyauthors
Ling ZD,Pieri SC,Carvey PMdoi
10.1097/00002826-199619040-00010subject
Has Abstractpub_date
1996-08-01 00:00:00pages
360-5issue
4eissn
0362-5664issn
1537-162Xjournal_volume
19pub_type
杂志文章abstract::A 40-year-old man with cervical dystonia developed an acute inflammatory demyelinating polyradiculoneuritis after botulinum toxin type A treatment. Some cases of idiopathic brachial plexopathy and polyradiculoneuritis have been reported to date. Although a causal relationship is not firmly established, the clinical te...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-200007000-00012
更新日期:2000-07-01 00:00:00
abstract:OBJECTIVES:Autism spectrum disorders (ASDs) have core impairments in social communication as well as the presence of repetitive, stereotypic behaviors and restricted interests. Older adolescents and young adults are particularly impacted by these deficits. Preclinical data implicate glutamatergic dysfunction in the pat...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/WNF.0000000000000033
更新日期:2014-05-01 00:00:00
abstract::Monoamine oxidase (MAO) inhibitors (MAOIs) provide effective alternative therapy for those patients with major depression who do not respond to tricyclic antidepressants or such related compounds as the selective serotonin reuptake inhibitors. This article reviews studies on the efficacy of both the classical MAOIs an...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1993-01-01 00:00:00
abstract::The mortality risk associated with cardiovascular disease is significantly increased in patients with major depression and panic disorder. The mechanism of this phenomenon is unclear. Thrombin is responsible for platelet aggregation and shape change, and it plays a significant role in the development of thromboembolic...
journal_title:Clinical neuropharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00002826-200007000-00002
更新日期:2000-07-01 00:00:00
abstract:ABSTRACT:Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. Methylphenidate (MPH) is one of the most widely used drugs in the treatment of ADHD. Enuresis can occur comorbidly with ADHD. However, enuresis is sometimes seen in patients with ADHD as an adve...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/WNF.0000000000000422
更新日期:2021-01-01 00:00:00
abstract::We describe a 78-year-old gentleman who, following bilateral above-knee amputations, developed symptoms of restless legs syndrome in the absent portions of his lower extremities. These symptoms improved with dopamine agonist therapy. In addition, he later developed parkinsonism with prominent rest tremor on metoclopra...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-200403000-00008
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:Serotonin syndrome is a potentially fatal complication that usually occurs in the combination use of several serotonergic agents. We presented a patient with major depressive disorder under the treatment of bupropion, trazodone, and quetiapine. Serotonin syndrome developed soon after she received the first s...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/WNF.0000000000000076
更新日期:2015-05-01 00:00:00
abstract::Venlafaxine (VEN) pharmacokinetics and effects on the brain monoamine output were investigated in the context of experimental hepatic encephalopathy (HE). Systemic VEN (10 mg/kg; subcutaneous) was administered to chronic portacaval shunted (PCS) and sham-operated rats. Their neocortical extracellular levels of 5-HT, 5...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract:OBJECTIVES:Paroxetine has been reported to be useful for management of stuttering symptoms, but only a few reports have examined its effects. We have investigated the efficacy of paroxetine in a randomized, placebo-controlled study. METHODS:Five stuttering subjects received paroxetine at 20 mg once daily at night for ...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/WNF.0b013e31819817eb
更新日期:2009-07-01 00:00:00
abstract:OBJECTIVE:To determine whether a history of depression predisposes hyperkinetic patients treated with tetrabenazine (TBZ) to a recurrence or worsening of this symptom. METHODS:We retrospectively reviewed the charts of 518 patients treated with TBZ to determine the frequency of depression and other adverse events. Char...
journal_title:Clinical neuropharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/01.WNF.0000228369.25593.35
更新日期:2006-09-01 00:00:00
abstract::In recent studies, disorders of chromatic and achromatic vision in parkinsonian patients have been demonstrated; these could be partially restored after application of L-Dopa. In this study, the effect of a 3-day infusion therapy with amantadine sulphate on color vision was evaluated in 19 parkinsonian patients by use...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-199510000-00009
更新日期:1995-10-01 00:00:00
abstract::Clinical trials with cholinergic agents suggest that cholinergic hypertrophy may be beneficial in the treatment of Alzheimer's disease (AD). Recent findings substantiate the view that nerve growth factor (NGF) selectively acts on cholinergic neurons. In adult rats and primates, intraventricular administration of nerve...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:10.1097/00002826-199114001-00008
更新日期:1991-01-01 00:00:00
abstract::Studies assessing the effect of transdermal nicotine in Parkinson's disease (PD) have generated mixed results regarding its efficacy to treat motor and cognitive deficits. These studies generally reported good tolerability in nonsmoking PD patients. The authors report the tolerability data of an open trial with transd...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-200309000-00004
更新日期:2003-09-01 00:00:00
abstract::Obsessive-compulsive disorder (OCD) is a brain disorder with recognizable periods of onset, course, familial occurrence, epidemiology, phenomenology, and treatment response. Several manifestations of pathophysiology are beginning to be defined, although they may represent intermediate pathophysiology rather than prima...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:10.1097/00002826-200107000-00002
更新日期:2001-07-01 00:00:00
abstract::The purpose of this paper is to add to the growing number of reports about kleptomania occurring in relation to brain injury as well as to present the authors' findings regarding treatment strategies. The authors present two case reports of patients who developed the new onset of kleptomania after closed head trauma. ...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/01.wnf.0000144042.66342.d3
更新日期:2004-09-01 00:00:00
abstract::A patient with melanoma and sporadic positive melanuria developed Parkinson's disease. Treatment with levodopa failed to modify tumoral progress. However, during chemotherapy with dacarbazine, the patient experienced a significant impairment to levodopa response. ...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-199202000-00010
更新日期:1992-02-01 00:00:00
abstract::The effects of the psychotropic drug etoperidone on the response to laboratory stressors was investigated in a controlled study. Cardiovascular and hormonal (catecholamines, corticotropin, and cortisol) measurements were made in a group of young, healthy volunteers during a cold pressor test (CPT), a mental arithmetic...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-199304000-00005
更新日期:1993-04-01 00:00:00
abstract::The capacity of peripheral blood mononuclear cells (PBMCs) of anorexia nervosa (AN) patients to produce interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-3-like activity (IL-3-LA) was studied. A significantly lower (-49%, p < 0.005) capacity to synthesize IL-2 and an almost significantly impaired ability (-3...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-199306000-00007
更新日期:1993-06-01 00:00:00
abstract::Five of 24 (21%) normal men (volunteers) administered alpha-methyl-para-tyrosine (AMPT), a catecholamine-depleting agent, developed acute dystonic reactions. The finding that catecholamine depletion without receptor blockade is sufficient to cause acute dystonia suggests that a variety of neurotransmitter imbalances m...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/00002826-199012000-00009
更新日期:1990-12-01 00:00:00
abstract:OBJECTIVES:IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on t...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/WNF.0000000000000126
更新日期:2016-01-01 00:00:00
abstract:OBJECTIVE:Although hormone replacement therapy (HRT) improves menopausal depressive symptoms, women unresponsive to HRT need an antidepressant drug as an effective adjunctive therapy. The aim of this study was to assess whether the herbal medicine Unkei-to has an impact on HRT-resistant menopausal depressive symptoms a...
journal_title:Clinical neuropharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/01.wnf.0000138634.34498.05
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:A multicenter open-label clinical trial was conducted to evaluate the clinical usefulness of topiramate (TPM) as primary or adjunctive therapy for infantile spasms in the postmarketing period in China. METHODS:Thirty-four centers participated in the trial. Patients included in the study had 1 or more seizure...
journal_title:Clinical neuropharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/WNF.0b013e3180986d43
更新日期:2008-03-01 00:00:00
abstract::Glutamate is the predominant excitatory neurotransmitter of the basal ganglia, where it acts on ionotropic and metabotropic receptors. In the best studied of the basal ganglia disorders, Parkinson's disease, there is compelling evidence that the activities of glutamatergic pathways are altered. Of particular importanc...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:10.1097/00002826-200103000-00001
更新日期:2001-03-01 00:00:00
abstract::A 51-year-old woman became depressed following the death of her father-in-law. She was given 50 mg of milnacipran a day. One week after starting milnacipran, she developed parkinsonism. The milnacipran was increased to 100 mg/d, resulting in a situation where her symptoms of parkinsonism and depression worsened, which...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:10.1097/WNF.0b013e31815947c7
更新日期:2008-09-01 00:00:00
abstract:OBJECTIVES:Aripiprazole and ziprasidone are 2 antipsychotic medications that are relatively devoid of the metabolic adverse effects associated with the second-generation antipsychotics. This study aimed to evaluate the effectiveness of switching to ziprasidone in patients who had insufficient response or intolerance to...
journal_title:Clinical neuropharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/WNF.0b013e3181d52b85
更新日期:2010-05-01 00:00:00
abstract::Male albino rats received a stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra. Animals demonstrating contralateral rotations 2 weeks postoperatively with apomorphine (0.5 mg/kg i.p.) were treated with L-Dopa (55 mg/kg i.p.), bromocriptine (2 mg/kg i.p.), or polyethylene glycol (vehicl...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::The treatment of obesity remains a puzzling challenge because long-term maintenance of weight loss--one of the most suitable goals--is rarely achieved with conventional methods. Among the theoretical measures able to maintain a permanent and bearable constraint to obtain the maintenance of weight loss is long-term (li...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1988-01-01 00:00:00
abstract::During long-term treatment of schizophrenia with antipsychotic medication, side effects such as weight gain and tardive dyskinesia may develop, while other extrapyramidal side effects may continue. A large multicenter, double-blind, comparative trial of haloperidol decanoate and fluphenazine decanoate has been complet...
journal_title:Clinical neuropharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1991-01-01 00:00:00
abstract::Therapeutic strategies in the treatment of dystonia consist primarily of pharmacologic, surgical, and supportive approaches. Many recent advances have been made in the treatment of dystonia with newer medications, availability of different botulinum toxins, and surgical procedures. However, these treatment modalities ...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:10.1097/00002826-200303000-00010
更新日期:2003-03-01 00:00:00
abstract::Flumazenil is a benzodiazepine receptor antagonist. It is currently used mainly in the anaesthetic and emergency rooms to reverse the effect of exogenous benzodiazepines. Its use in a variety of experimental animal models and in human neuropsychiatric disorders continues to generate a wealth of information on the poss...
journal_title:Clinical neuropharmacology
pub_type: 杂志文章,评审
doi:10.1097/00002826-199506000-00002
更新日期:1995-06-01 00:00:00