Abstract：
:Major depression is a highly prevalent disorder and is predicted to be the second leading cause of disease burden by 2020. Although many antidepressant drugs are currently available, they are far from optimal. Approximately 50% of patients do not respond to initial first line antidepressant treatment, while approximately one third fail to achieve remission following several pharmacological interventions. Furthermore, several weeks or months of treatment are often required before clinical improvement, if any, is reported. Moreover, most of the commonly used antidepressants have been primarily designed to increase synaptic availability of serotonin and/or noradrenaline and although they are of therapeutic benefit to many patients, it is clear that other therapeutic targets are required if we are going to improve the response and remission rates. It is clear that more effective, rapid-acting antidepressants with novel mechanisms of action are required. The purpose of this review is to outline the current strategies that are being taken in both preclinical and clinical settings for identifying superior antidepressant drugs. The realisation that ketamine has rapid antidepressant-like effects in treatment resistant patients has reenergised the field. Further, developing an understanding of the mechanisms underlying the rapid antidepressant effects in treatment-resistant patients by drugs such as ketamine may uncover novel therapeutic targets that can be exploited to meet the Olympian challenge of developing faster, better and stronger antidepressant drugs.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
O'Leary OF,Dinan TG,Cryan JFdoi
10.1016/j.ejphar.2014.07.046subject
Has Abstractpub_date
2015-04-15 00:00:00pages
32-50eissn
0014-2999issn
1879-0712pii
S0014-2999(14)00584-6journal_volume
753pub_type
杂志文章,评审abstract：:The effects of an inhibitor of calmodulin, trifluoperazine (TFP), were determined on the electrical activity of cultured cell reaggregates derived from chick embryonic hearts (15-day-old). The cells exhibited naturally occurring slowly rising action potentials (APs) having a maximum rate of rise (+Vmax) of less than 3...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90645-9
更新日期：1984-10-01 00:00:00
abstract：:We reported previously that 18 compounds varying in general anesthetic potency by up to 66 000-fold inhibited, at anesthetic concentrations, the metabolism of arachidonic acid and aminopyrine by cytochrome P450 monooxygenases in rat liver microsomes. Now, we report that P450-mediated para-hydroxylation of aniline is m...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)00022-4
更新日期：1995-10-06 00:00:00
abstract：:The (+) and (-) enantiomers of the substituted 2-aminotetralin, N-0437 were evaluated in vivo for their dopaminergic activity, using biochemical as well as behavioural models. In presynaptic models, i.e. antagonism of gamma-butyrolactone-induced dihydroxyphenylalanine elevations and the induction of hypomotility, both...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90309-3
更新日期：1988-02-09 00:00:00
abstract：:Histamine stimulated the accumulation of [3H]inositol 1-phosphate in the presence of lithium in [3H]inositol-prelabelled slices from rat brain cortex in a concentration-dependent manner, with an EC50 value of 94.7 microM. High concentrations of antagonists of histamine H2 receptors, muscarinic receptors, alpha 1-adren...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90659-x
更新日期：1986-04-16 00:00:00
abstract：:The effect of a novel leuktriene B4 receptor antagonist N-[5[[8-(1-hydroxy-2- phenyl)ethyl]dibenzofuran-2yl]5-hydroxypentanoyl]pyrrolidine (PF 10042) has been evaluated in comparison with 2-[3(1-hydroxyhexyl)phenoxymethyl]quinoline hydrochloride (PF 5901), a specific inhibitor of the 5-lipoxygenase pathway of arachido...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90057-8
更新日期：1995-12-07 00:00:00
abstract：:In isolated, perfused rabbit ear artery bradykinin, like [Met5]enkephalin and angiotensin II, inhibited neurogenic constrictions in concentrations lower than 10(-8) M without affecting the responses to exogenous norepinephrine. The IC50 value of bradykinin was 1.95 x 10(-10) M. The inhibitory action of bradykinin and ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90567-a
更新日期：1991-05-30 00:00:00
abstract：:Procaine and procainamide were covalently bound to acryloyl monomers and polymers. The dose-response and time-action parameters of the cardiac antiarrhythmic protection afforded by the prototype drugs and their acryloyl derivatives against chloroform-hypoxia-induced cardiac arrhythmias in unanesthetized mice and epine...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90367-x
更新日期：1985-08-27 00:00:00
abstract：:The protective effect of coenzyme Q10 against testicular toxicity induced by sodium arsenite (10mg/kg/day, orally for two consecutive days) was investigated in rats. Coenzyme Q10 treatment (10mg/kg/day, i.p.) was applied for five consecutive days, starting three days before arsenite administration. Coenzyme Q10 signif...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.12.045
更新日期：2011-03-25 00:00:00
abstract：:Acid-sensing ion channels (ASICs) are involved in numerous physiological and pathological processes in the central nervous system. Development of pharmacological tools capable to inhibit or potentiate these channels is important for our knowledge about roles of ASICs in the neuronal network and can be promising for tr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.06.013
更新日期：2016-10-05 00:00:00
abstract：:Cutaneous arteries show enhanced contraction in response to cooling, which is suggested to be mediated via α2C-adrenoceptors. We have previously shown that α1-adrenoceptors are also involved in the enhanced contraction in cooling conditions. In the present study, we aimed to identify the α1-adrenoceptor subtype involv...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.09.004
更新日期：2018-11-05 00:00:00
abstract：:In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.07.003
更新日期：2015-10-05 00:00:00
abstract：:Sibutramine was formerly marketed as an anti-obesity agent. The current study investigated the relationships between monoamine reuptake site occupancy for sibutramine and both its antidepressant-like efficacy and thermogenic effects. Sibutramine's effects on locomotor activity (LMA) and food intake were also evaluated...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.03.024
更新日期：2014-08-15 00:00:00
abstract：:Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Mast cells (MCs) are located perivascularly close to neurons and microglia, primarily in the leptomeninges, thalamus, hypothalamus and especially the median eminence. Corticotropin-releasing factor (CRF)...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.03.086
更新日期：2016-05-05 00:00:00
abstract：:The cerebral circulation is innervated by calcitonin gene-related peptide (CGRP) containing fibers originating in the trigeminal ganglion. During a migraine attack, there is a release of CGRP in conjunction with the head pain, and triptan administration abolishes both the CGRP release and the pain at the same time. In...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00934-1
更新日期：2001-03-09 00:00:00
abstract：:The effect of aclarubicin on vasocontractility was investigated using aortic strips isolated from rats. The aortic strips from rats injected i.p. with aclarubicin (4 mg/kg body weight per day for 5 consecutive days) showed diminished contractile responses to KCl and phenylephrine in comparison with the controls inject...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90761-9
更新日期：1989-08-11 00:00:00
abstract：:The monoethyl, monopropyl and monoisopropyl esters of succinic acid, administered intravenously at the dose of 2 micromol/g body weight, were found to increase the insulinotropic action of gliquidone (0.2 nmol/g body weight) in anaesthetized rats. The monoisopropyl ester of succinic acid also doubled the hypoglycemic ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)00099-x
更新日期：1997-04-23 00:00:00
abstract：:We have previously found that the induction of long-term potentiation in the synaptic pathway from the basolateral amygdala to the dentate gyrus (BLA-DG LTP) is regulated by L-type Ca(2+) channels, dopamine D(2) receptors and GABAergic inhibition. In the present study, we investigated possible relations among the thre...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.01.017
更新日期：2009-03-15 00:00:00
abstract：:In the presence of thiorphan an 'enkephalinase' inhibitor, bestatin an aminopeptidase inhibitor of bacterial origin potently inhibited the hydrolysis of [3H][Leu5]enkephalin by slices from rat striatum with an IC50 value of about 0.2 microM whereas puromycin was approximately 1000 times less potent on this preparation...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90181-4
更新日期：1983-01-21 00:00:00
abstract：:The effects of systemic administration of the full dopamine D1 receptor agonist A-77636 on acetylcholine release in rat frontal cortex and hippocampus were studied using in vivo microdialysis. Administration of A-77636 (4 mumol/kg s.c.) greatly (> 230%) increased both cortical and hippocampal acetylcholine release for...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90013-2
更新日期：1994-07-21 00:00:00
abstract：:Painless myocardial infarction is a serious complication of diabetes. The present study examined whether cardiac nociception was altered in the streptozotocin-induced diabetic rat model by assessing intrapericardial capsaicin-evoked electromyography (EMG) responses in the spinotrapezius muscle. Somatic sensitivities t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.10.073
更新日期：2011-01-25 00:00:00
abstract：:To test whether polytherapy with two gamma-aminobutyric acid (GABA) -ergic drugs might be clinically relevant for epilepsy treatment, effects on spike and wave discharges, the fraction of time spent being behaviourally active, and the background electroencephalogram (EEG) during behavioural activity of vigabatrin (15-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.05.027
更新日期：2004-07-14 00:00:00
abstract：:The effect of nimodipine was studied on EEG power density spectra as well as on 31P-NMR spectra of the brain before, during and after four-vessel occlusion (FVO) in the restrained conscious rat. EEG-spectral analysis: eight rats were submitted to 5 min FVO and four of them received nimodipine (1 mg/kg orally) 75 min b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90799-5
更新日期：1986-06-24 00:00:00
abstract：:Endothelial cells from rat brain microvessels, human aortic artery and human umbilical vein were examined, together with ex vivo rat brain capillaries and rat aortic ring sections, for the expression of opioid receptor-like OP-4 mRNA and protein. High levels of mRNA expression and an immunopositive reaction for the re...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.09.049
更新日期：2003-12-15 00:00:00
abstract：:High pressure liquid chromatography (HPLC) combined with radiochemical detection was used to show that [3H]noradrenaline (NA) and [14C]ATP were released concomitantly during field stimulation of the rat vas deferens. The release of radioactivity (3H and 14C) in response to three consecutive field stimulations was cons...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90254-3
更新日期：1988-12-06 00:00:00
abstract：:The kinetics of receptor blockade by chlorpromazine (5 X 10(-8) M) were studied on fundic strips from the rabbit stomach. Onset of blockade by chlorpromazine proceeds at nearly identical rates when carbamylcholine and histamine are the agonists (t1/2 = approximately 5 min) while occurring more slowly against phenyleph...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90324-2
更新日期：1978-03-15 00:00:00
abstract：:Alzheimer's disease is the most frequent cause of dementia. Family and twin studies have suggested that genetic factors play a role in Alzheimer's disease development. Some Alzheimer's disease cases show an autosomal dominant inheritance pattern and thus allow the discovery of major disease genes. However, most Alzhei...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0014-2999(00)00903-1
更新日期：2001-01-19 00:00:00
abstract：:Insulin resistance is a causative factor for type 2 diabetes, whereas the development of insulin resistance is closely related to chronic inflammation induced by factors such as tumor necrosis factor-α (TNF-α). Momordica charantia, also known as bitter melon, has been used as an herbal medicine and reported to amelior...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.05.033
更新日期：2012-08-15 00:00:00
abstract：:Ginsenoside Rg3 (Rg3), one of the bioactive extracts found in ginseng root, was reported to have anti-cancer activity in various cancer models. The anti-proliferation effect of Rg3 on prostate cancer cells has been well reported. To test whether Rg3 has an anti-metastatic effect on prostate cancer, we treated a highly...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.02.040
更新日期：2012-05-15 00:00:00
abstract：:Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addition to opiate and stimulant drugs. As a preclinical test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administration of morphine in rats. Ibogaine dose dependently (2.5-80 m...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90474-5
更新日期：1991-04-03 00:00:00
abstract：:Omega-3 polyunsaturated fatty acids have been reported to be associated with favorable changes in the respiratory system. To determine one of the mechanisms for this effect, membrane currents were recorded in guinea-pig tracheal myocytes by using the whole-cell voltage clamp technique. Without EGTA in the patch pipett...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00484-1
更新日期：1998-08-21 00:00:00
