Abstract：
:Despite the revolution in recent decades regarding monoamine involvement in the management of major depressive disorder (MDD), the biological mechanisms underlying this psychiatric disorder are still poorly understood. Currently available treatments require long time courses to establish antidepressant response and a significant percentage of people are refractory to single drug or combination drug treatment. These issues, and recent findings demonstrating the involvement of synaptic plasticity in the pathophysiological mechanisms of MDD, are encouraging researchers to explore the molecular mechanisms underlying psychiatric disease in more depth. The discovery of the rapid antidepressant effect exerted by glutamatergic and cholinergic agents highlights the mammalian target of rapamycin (mTOR) pathway as a critical pathway that contributes to the efficacy of these pharmacological agents in clinical and pre-clinical research. The mTOR pathway is a downstream intracellular signal that transmits information after the direct activation of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and neurotrophic factor receptors. Activation of these receptors is hypothesized to be one of the major axes involved in the synthesis of synaptogenic proteins underlying synaptic plasticity and critical to both the rapid and delayed effects exerted by classic antidepressants. This review focuses on the involvement of mTOR in the pathophysiology of depression and on molecular mechanisms involved in the activity of emerging and classic antidepressant agents.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Ignácio ZM,Réus GZ,Arent CO,Abelaira HM,Pitcher MR,Quevedo Jdoi
10.1111/bcp.12845subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1280-1290issue
5eissn
0306-5251issn
1365-2125journal_volume
82pub_type
杂志文章,评审abstract：:Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine cha...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1992.tb04048.x
更新日期：1992-03-01 00:00:00
abstract：:1. The effects of a single oral dose of enalapril 10 mg on serum ACE activity and blood pressure in relation to the ACE genotype were studied in 27 healthy men, n = 9 each of genotype DD, ID and II, in a parallel group study design. 2. Before treatment serum ACE activity differed significantly between the genotypes, w...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1995.tb04419.x
更新日期：1995-02-01 00:00:00
abstract：:We have developed a method of monitoring plasma concentrations of antiepileptic drugs which uses salivary samples, and is suitable for home monitoring in children. To validate the method, paired plasma and saliva samples from 39 children aged between 2 and 15 years were assayed for carbamazepine and its active metabol...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1993.tb05700.x
更新日期：1993-03-01 00:00:00
abstract：AIMS:Carbamazepine (CBZ) is an inducer of cytochrome P450 enzymes, which have been implicated in many drug interactions. However, for immunosuppressant and anti-HIV drugs, whose main site of action is the lymphocyte, induction of P-glycoprotein (Pgp) may also be important. In this study, we have investigated whether CB...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02587.x
更新日期：2006-08-01 00:00:00
abstract：:The acute peripheral vascular and diuretic effects of intravenous frusemide 10 mg and 20 mg were compared with those of bumetanide 250 micrograms and 500 micrograms in a group of 10 salt depleted volunteers. Significant reductions in forearm blood flow (FBF) were observed after frusemide 10 mg (-0.77 ml 100 ml-1 min-1...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1986.tb05207.x
更新日期：1986-04-01 00:00:00
abstract：AIMS:Changes in both digoxin and aciclovir renal clearance following coadministration with some other renally eliminated drugs have been reported. The potential interaction of valaciclovir, with its antiherpetic metabolite aciclovir, and digoxin was investigated. METHODS:Twelve healthy volunteers (seven males, five fe...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1998.00649.x
更新日期：1998-01-01 00:00:00
abstract：:The dose-response effects of oral nicardipine on the systemic blood pressure were examined in 54 patients with uncomplicated essential hypertension (DBP greater than or equal to 100 mm Hg). The study was designed in four sequential stages. A 2 week single-blind placebo run-in period was followed by dose titration with...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1985.tb05156.x
更新日期：1985-01-01 00:00:00
abstract：AIM:We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. METHODS:A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) w...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.12294
更新日期：2014-06-01 00:00:00
abstract：:1. The N-acetylation of dapsone (DDS) was studied in 182 unrelated healthy Japanese subjects. The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS, slow acetylators less than 0.30 and rapid acetylators greater than 0.35) at 3 h after an oral dose of DDS (100 m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb03333.x
更新日期：1988-04-01 00:00:00
abstract：:The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA). At baseline a complete haemodynamic profile, including cardiac output and coronary sinus blood flow (CSBF) wa...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1995.tb04491.x
更新日期：1995-05-01 00:00:00
abstract：:1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1994.tb04268.x
更新日期：1994-03-01 00:00:00
abstract：:1. The possibility of a pharmacokinetic interaction between the H2-receptor antagonist cimetidine and the long-acting local anaesthetic agent bupivacaine was studied in seven healthy, non-smoking volunteers. 2. The study consisted of two sessions at a minimum interval of 4 days. In a randomized, crossover fashion, the...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1988.tb03398.x
更新日期：1988-10-01 00:00:00
abstract：AIMS:Although cysteamine was first used in the treatment of cystinosis in 1976 and approved by the FDA as cysteamine bitartrate (Cystagon) in 1994, surprisingly little pharmacological data are available for this compound. Cysteamine and its related drugs are currently being evaluated for the treatment of Huntington's a...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02734.x
更新日期：2007-01-01 00:00:00
abstract：AIMS:Potassium channel openers (KCOs) are of potential therapeutic value. Little is known about the effect of these drugs on human conduit arteries used as coronary bypass grafts. The purpose of this study was to determine the effect of the KCO aprikalim (RP52891) on human arteries used as coronary bypass grafts with e...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1997.00640.x
更新日期：1997-10-01 00:00:00
abstract：:1. The cardiovascular responses of mianserin hydrochloride and tricyclic antidepressant drugs were investigated using non-invasive methods of cardiac investigation. A study of the interaction of mianserin and antihypertensive drug therapy is reported. 2. In six normal volunteers, mianserin hydrochloride 20 mg was show...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1978-01-01 00:00:00
abstract：:In a double-blind, placebo-controlled, randomised, cross-over study of six healthy male subjects, the effect of nicardipine (5 mg h-1 for 3 h) on basal and stimulated pituitary hormone release was examined. Statistically significant differences between nicardipine and placebo were seen occasionally for follicle-stimul...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1985.tb05147.x
更新日期：1985-01-01 00:00:00
abstract：AIM:To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODS:Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outco...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04208.x
更新日期：2012-08-01 00:00:00
abstract：AIMS:To study the effect of eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, on digoxin pharmacokinetics in a randomized, open-label, two period, period balanced crossover study in 12 healthy men. METHODS:Each subject received a single 0.6 mg oral dose of digoxin (Lanoxicaps 0.2 mg/capsule, Glax...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1997.00608.x
更新日期：1997-06-01 00:00:00
abstract：:1. The attitudes of general practitioners and hospital physicians to the management of hypertension in the elderly, were examined by responses to a postal questionnaire distributed within the Northern Region, concerning the management of a healthy 75 year old male non-smoker with sustained diastolic or isolated systol...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1995.tb04481.x
更新日期：1995-05-01 00:00:00
abstract：AIMS:We investigated the effect of angiotensin converting enzyme inhibitors (ACEIs) on postsynaptic adrenoceptor sensitivity and compared the effect of the lipophilic ACEI, quinapril, and that of hydrophilic agent, enalapril in human vessels. METHODS:Alpha-adrenoceptor sensitivity was evaluated using the dorsal hand v...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.1998.00834.x
更新日期：1998-12-01 00:00:00
abstract：:1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with ea...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1989.tb03512.x
更新日期：1989-07-01 00:00:00
abstract：AIM:We investigated whether moxifloxacin-induced QTc prolongations in Japanese and Caucasian healthy male volunteers were significantly different. METHODS:A two period, randomized, crossover, ICH-E14-compliant thorough QT (TQT) study compared placebo-corrected changes in QTc interval from baseline (ΔΔQTc F) and concen...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.12684
更新日期：2015-09-01 00:00:00
abstract：:1. Apomorphine (1 and 5 micrograms kg-1) and placebo were given to nine normal volunteers, using a Latin-square design and double-blind procedures. The visual perception of static and moving patterns (static and motion contrast sensitivity) was evaluated before and 15 min after the dose administration. 2. Apomorphine ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1991.tb03950.x
更新日期：1991-11-01 00:00:00
abstract：:1. Endogenous dopamine, acting through specific receptors on blood vessels, renal tubules and adrenal cortical cells, may play a role in the development and maintenance of the hypertensive state. 2. In hypertensive patients, activation of the DA1-receptor with intravenous fenoldopam produces a rapid and sustained redu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.1990.tb05470.x
更新日期：1990-01-01 00:00:00
abstract：:1. The relationship between the metabolism of the antiarrhythmic drug mexiletine and the debrisoquine/sparteine-type polymorphism was studied in vitro, using microsomes from six human livers, and in vivo, in nine healthy drug-free volunteers with wide variation in their ability to hydroxylate debrisoquine. 2. There wa...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb03931.x
更新日期：1991-10-01 00:00:00
abstract：:1. The purpose of this study was to evaluate possible changes in brain morphology and evoked potentials associated with daily administration of 300 mg kg-1 vigabatrin in dogs. 2. Somatosensory evoked potentials (SEP) and auditory evoked potentials (AEP) were recorded at baseline and weekly for 12 weeks of treatment an...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03462.x
更新日期：1989-01-01 00:00:00
abstract：:Cytochrome P450 3A is the main enzyme subfamily involved in the metabolism of a variety of marketed medicines. It is generally believed that the substrate specificity of polymorphic P450 3A5 is similar to that of the predominant P450 3A4 isoform, although some differences in catalytic properties have been found. It ha...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03656.x
更新日期：2010-06-01 00:00:00
abstract：:1. Double-blind controlled comparisons of nomifensine with placebo, imipramine, desipramine, viloxazine, nortriptyline, a combination of amitriptyline and chlordiazepoxide, and diazepam have been carried out in various parts of the world. 2. Dosage ranged from 50-225 mg daily, and treatment lasted from 2-26 weeks. 3. ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,评审
doi：10.1111/j.1365-2125.1977.tb05759.x
更新日期：1977-01-01 00:00:00
abstract：:Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibula...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14046
更新日期：2019-10-01 00:00:00
abstract：:1. The phenotyping parameters for dextromethorphan and mephenytoin were assessed in 48 normal male volunteers following administration of each metabolic probe drug on separate occasions and together according to a randomized 3-way crossover design. 2. Neither the urinary S-/R-mephenytoin ratio nor the dextromethorphan...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1990.tb03653.x
更新日期：1990-04-01 00:00:00
