Perspectives on the mGluR2/3 agonists as a therapeutic target for schizophrenia: Still promising or a dead end?

Abstract:

:Group II metabotropic glutamate receptor (mGluR2/3) agonists once showed promise as non-dopaminergic antipsychotic drugs because of their efficacy in alleviating symptoms of schizophrenia (SZ) in both animal models and human patients. However, the recent failure of Phase III clinical trials dealt a huge blow to the scientific community and the aftershock of the setback in mGluR2/3 research can be felt everywhere from grant support and laboratory studies to paper publication. An immediate question raised is whether mGluR2/3 is still a promising therapeutic target for schizophrenia. Answering this question is not easy, but apparently a new strategy is needed. This article provides a focused review of literature on the study of mGluR2/3 agonists, especially on mGluR2/3 agonists' mechanism of action and efficacy in both normal conditions and animal models of SZ, as well as clinical studies in human patients with the disease. We argue that the cellular and molecular actions of mGluR2/3 agonists, the distinct roles between mGluR2 and mGluR3, as well as their effects on different stages of the disease and different subpopulations of patients, remain incompletely studied. Until the mechanisms associated with mGluR2/3 are clearly elucidated and all treatment options are tested, it would be a great mistake to terminate the study of mGluR2/3 as a therapeutic target for schizophrenia. This review will thus shed light on the comprehensive features of the translational potential mGluR2/3 agonists as well as the need for further research into the more selective activation of mGluR2.

authors

Li ML,Hu XQ,Li F,Gao WJ

doi

10.1016/j.pnpbp.2015.02.012

subject

Has Abstract

pub_date

2015-07-03 00:00:00

pages

66-76

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(15)00045-7

journal_volume

60

pub_type

杂志文章,评审
  • Protein kinase C, learning and memory: a circular determinism between physiology and behaviour.

    abstract::1. In vertebrates as in invertebrates, protein kinase C appears to have a key role in learning and memory, probably given its involvement in synaptic plasticity. 2. Hippocampal PKC in mammalians is activated by learning in a large variety of memory tasks. However, the kind of information processed, the type of task, a...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/s0278-5846(97)00015-8

    authors: Noguès X

    更新日期:1997-04-01 00:00:00

  • Early intervention with electroacupuncture prevents PTSD-like behaviors in rats through enhancing hippocampal endocannabinoid signaling.

    abstract::Electroacupuncture (EA) is a clinically useful physiological therapy that has been recently adopted to treat several brain disorders. However, the potential role of early EA intervention in the prevention of posttraumatic stress disorder (PTSD) as well as its potential cellular and molecular mechanism has never been i...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2019.03.018

    authors: Xue F,Xue SS,Liu L,Sang HF,Ma QR,Tan QR,Wang HN,Zhou CH,Peng ZW

    更新日期:2019-07-13 00:00:00

  • Effects of pertussis toxin on behavioral responses during different withdrawal periods from chronic cocaine treatment.

    abstract::1. The role of Gi-proteins on cataleptic responses induced by SCH23390 and haloperidol in chronic cocaine-treated mice was examined by intracerebroventricullor (i.c. v.) and intravenous (i. v.) injections of pertussis toxin (PTX), which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins. 2. In animals p...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/s0278-5846(00)00134-2

    authors: Ushijima I,Mizuki Y,Kobayashi T,Aoki T,Suetsugi M,Usami K,Watanabe Y

    更新日期:2000-11-01 00:00:00

  • Inhibition of central angiotensin II enhances memory function and reduces oxidative stress status in rat hippocampus.

    abstract::While it is now well established that the independent brain renin-angiotensin system (RAS) has some important central functions besides the vascular ones, the relevance of its main bioactive peptide angiotensin II (Ang II) on the memory processes, as well as on oxidative stress status is not completely understood. The...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2012.12.009

    authors: Bild W,Hritcu L,Stefanescu C,Ciobica A

    更新日期:2013-06-03 00:00:00

  • The effects of postnatal handling on the development of the glucocorticoid receptor systems and stress recovery in the rat.

    abstract::We have examined the effects of postnatal handling of rat pups from Days 1 to 21 on the development of the intracellular, glucocorticoid receptor in the hippocampus, and pituitary transcortin, and corticoid binding globulin in plasma. All animals were sacrificed 10-14h following adrenalectomy and the in vitro receptor...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/0278-5846(85)90050-8

    authors: Meaney MJ,Aitken DH,Bodnoff SR,Iny LJ,Sapolsky RM

    更新日期:1985-01-01 00:00:00

  • Effects of antipsychotic D2 antagonists on long-term potentiation in animals and implications for human studies.

    abstract::In people with schizophrenia, cognitive abilities - including memory - are strongly associated with functional outcome. Long-term potentiation (LTP) is a form of neuroplasticity that is believed to be the physiological basis for memory. It has been postulated that antipsychotic medication can impair long-term potentia...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/j.pnpbp.2014.05.001

    authors: Price R,Salavati B,Graff-Guerrero A,Blumberger DM,Mulsant BH,Daskalakis ZJ,Rajji TK

    更新日期:2014-10-03 00:00:00

  • Iron, melanin and dopamine interaction: relevance to Parkinson's disease.

    abstract::1. Interaction between iron and melanin may provide a reasonable explanation for the vulnerability of the melanin containing dopaminergic neurons in the substantia nigra (SN) to neurodegeneration in Parkinson's disease (PD). 2. Scatchard analysis of the binding of iron to synthetic dopamine melanin revealed a high-aff...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/0278-5846(93)90038-t

    authors: Ben-Shachar D,Youdim MB

    更新日期:1993-01-01 00:00:00

  • Interferon: a candidate as the endogenous substance preventing tolerance and dependence to brain opioids.

    abstract::It has been suggested that protein synthesis and immunological factors play a role in the development of tolerance and dependence to opiates. Interferon (IFN) is known to influence protein synthesis and the immune system. Our and other data suggest that IFN may be an agent that prevents the development of tolerance an...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:

    authors: Dafny N

    更新日期:1984-01-01 00:00:00

  • Scopolamine-physostigmine combination does not substitute for nicotine.

    abstract::1. Male Sprague-Dawley rats were trained to discriminate 0.4 mg/kg nicotine subcutaneously administered from its saline vehicle in a food-motivated operant discrimination task. Once trained, the discriminative performance was observed to be dose-responsive with an ED50 = 0.11 mg/kg. 2. The co-administration of 0.1 or ...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/0278-5846(95)00030-y

    authors: Schechter MD

    更新日期:1995-05-01 00:00:00

  • Anti-inflammatory treatment in schizophrenia.

    abstract::Antipsychotics, which act predominantly as dopamine D2 receptor antagonists, have several shortcomings. The exact pathophysiological mechanism leading to dopaminergic dysfunction in schizophrenia is still unclear, but inflammation has been postulated to be a key player in the pathophysiology of the disorder. A dysfunc...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/j.pnpbp.2012.11.008

    authors: Müller N,Myint AM,Krause D,Weidinger E,Schwarz MJ

    更新日期:2013-04-05 00:00:00

  • Trends in searching for new cognition enhancing drugs.

    abstract::1. The great interest for new drugs having cognition enhancing properties is highlighted, particularly for the treatment of dementia of Alzheimer type. 2. A short survey is given of the pharmacological models currently used to mimic cognitive impairment. 3. A systematic survey is given of the major cognition enhancing...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/0278-5846(89)90111-5

    authors: Merlini L,Pinza M

    更新日期:1989-01-01 00:00:00

  • Regulation of dopamine release and metabolism in rat striatum in vivo: effects of dopamine receptor antagonists.

    abstract::1. The acute effects of some of typical and atypical antipsychotic drugs on the dopamine release and metabolism in the dorsal striatum of freely moving rats were studied using transcerebral microdialysis technique. 2. Classical neuroleptic drugs haloperidol (0.05, 0.1 and 0.2 mg/kg), thioproperazine (0.1, 0.2 and 0.4 ...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/0278-5846(95)00267-7

    authors: Rayevsky KS,Gainetdinov RR,Grekhova TV,Sotnikova TD

    更新日期:1995-12-01 00:00:00

  • Regulation of beta-amyloid precursor protein and inositol 1,4,5-trisphosphate receptor gene expression during differentiation of a human neuronal cell line.

    abstract::Retinoic acid-induced differentiation of SH-SY5Y human neuroblastoma cells results in the development of extensive neurite processes as well as changes in cell body morphology toward a neuronal phenotype. The authors have examined concurrent regulation of beta-amyloid precursor protein (APP) and inositol 1,4,5-trispho...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/S0278-5846(02)00352-4

    authors: Murray JN,Igwe OJ

    更新日期:2003-05-01 00:00:00

  • Pathophysiology in the comorbidity of Bipolar Disorder and Alzheimer's Disease: pharmacological and stem cell approaches.

    abstract::Neuropsychiatric disorders involve various pathological mechanisms, resulting in neurodegeneration and brain atrophy. Neurodevelopmental processes have shown to be critical for the progression of those disorders, which are based on genetic and epigenetic mechanisms as well as on extrinsic factors. We review here commo...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/j.pnpbp.2017.04.033

    authors: Corrêa-Velloso JC,Gonçalves MC,Naaldijk Y,Oliveira-Giacomelli Á,Pillat MM,Ulrich H

    更新日期:2018-01-03 00:00:00

  • Changes in EEG, blood levels, mood scales and performance scores during long term treatment with diazepam, phenobarbital or placebo in patients.

    abstract::1. The patient population consisting of fifteen patients was divided into three groups, namely: diazepam group, phenobarbital group and placebo group. After three weeks the medicated groups were switched to placebo for a week and the placebo group was given phenobarbital. 2. The parameters to be assessed once a week c...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0278-5846(82)80175-9

    authors: Schwarz E,Kielholz P,Hobi V,Goldberg L,Hofstetter M,Ladewig D

    更新日期:1982-01-01 00:00:00

  • Limbic control of aggression in the cat.

    abstract::Over a decade of work by Flynn and colleagues has delineated a network of limbic circuits which function to modulate the expression of predatory aggression and defence in the cat, and aspects of this work are reviewed. In particular, Flynn's work revealed a circuit involving the basomedial amygdala which functions to ...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/0278-5846(83)90017-9

    authors: Adamec RE,Stark-Adamec CI

    更新日期:1983-01-01 00:00:00

  • Increasing the density of the D2L receptor and manipulating the receptor environment are required to evidence the partial agonist properties of aripiprazole.

    abstract::The clinical efficacy of aripiprazole in the treatment of psychosis relies on a partial agonism at D2 receptors. As the expression of this receptor differs physiologically between pre- and post-synaptic sites and is affected by pathological conditions or pharmacological treatments, it appears difficult to predict the ...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2011.08.007

    authors: Koener B,Focant MC,Bosier B,Maloteaux JM,Hermans E

    更新日期:2012-01-10 00:00:00

  • VEGF serum levels in depressed patients during SSRI antidepressant treatment.

    abstract::Recent evidence indicates that the vascular endothelial growth factor (VEGF) may be involved in the neuronal mechanisms underlying both the depression aetiology and the response to pharmacological and non pharmacological antidepressant treatments. To investigate whether VEGF peripheral levels are altered in depression...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2008.11.009

    authors: Ventriglia M,Zanardini R,Pedrini L,Placentino A,Nielsen MG,Gennarelli M,Bocchio-Chiavetto L

    更新日期:2009-02-01 00:00:00

  • Potentiation of synaptic transmission by (S)-3,5-dihydroxy phenylglycine in the rat dentate gyrus in vitro: a role for voltage dependent calcium channels and protein kinase C.

    abstract::1. The authors have previously shown that direct activation of metabotropic glutamate receptors (mGluRs) by (S)-3,5-dihydroxyphenylglycine ((S)-DHPG) can induce a long-lasting potentiation of synaptic transmission in the rat dentate gyrus in vitro. Here the authors provide further characterisation of this agonist-indu...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/s0278-5846(98)00095-5

    authors: O'Leary DM,O'Connor JJ

    更新日期:1999-01-01 00:00:00

  • Pharmacotherapy for major depression in children and adolescents.

    abstract::Major depression is a serious illness in children which adversely effects their social, academic, and emotional development. It is essential to identify safe and effective medication for the treatment of this disorder in youths. Only some selective serotonin reuptake inhibitors (citalopram, fluoxetine, sertraline) hav...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/j.pnpbp.2005.03.005

    authors: Wagner KD

    更新日期:2005-06-01 00:00:00

  • Behavioral modifications in relation to hypothyroidism and hyperthyroidism in adult rats.

    abstract::1. Behavioural experiments were carried out on adult rats made hypothyroid and hyperthyroid. The hypothyroid rats in an "open field" situation reduced the number of squares crossed and boluses defecated, the hyperthyroid rats reduced the number of squares crossed. A swimming endurance was conducted to evaluate the phy...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/0278-5846(89)90044-4

    authors: Fundaro A

    更新日期:1989-01-01 00:00:00

  • A double-blind evaluation of zimelidine in comparison to placebo and amitriptyline in patients with major depressive disorder.

    abstract::This paper presents the results from a large multicenter study, performed at three clinical research units in the USA. Prior to a three to seven days of placebo washout period, patients were randomly assigned to zimelidine, a potent and selective 5-HT reuptake blocker, amitriptyline or placebo. The scheduled treatment...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/0278-5846(83)90125-2

    authors: Claghorn J,Gershon S,Goldstein BJ,Behrnetz S,Bush DF,Huitfeldt B

    更新日期:1983-01-01 00:00:00

  • Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response.

    abstract::Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic va...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2009.02.020

    authors: Tsai SJ,Hong CJ,Liou YJ,Yu YW,Chen TJ,Hou SJ,Yen FC

    更新日期:2009-06-15 00:00:00

  • The acute and residual effects of escalating, analgesic-range doses of ketamine on driving performance: A simulator study.

    abstract::Ketamine hydrochloride elicits potent psychotomimetic and neurobehavioural effects which make it incompatible with driving; however, the direct effect on driving performance is yet to be assessed. Using an open label, within-subjects protocol, 15 males and 5 females (mean age = 30.8 years) were administered three fixe...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2018.05.015

    authors: Hayley AC,Green M,Downey LA,Stough CKK,Keane M,Shiferaw B,Kostakis P,Shehabi Y

    更新日期:2018-08-30 00:00:00

  • More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia.

    abstract::Enhancement of neurocognition is essential in the treatment of schizophrenia. In our previously reported six-week randomized controlled trial (RCT) mirtazapine added to conventional antipsychotics improved not only negative, but also positive symptoms and neurocognition in difficult-to-treat schizophrenia. The present...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.pnpbp.2011.03.004

    authors: Stenberg JH,Terevnikov V,Joffe M,Tiihonen J,Tchoukhine E,Burkin M,Joffe G

    更新日期:2011-06-01 00:00:00

  • Effects of ethanol on nicotine-induced conditioned place preference in C57BL/6J mice.

    abstract::It has been shown that small doses of ethanol (

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2006.04.024

    authors: Korkosz A,Zatorski P,Taracha E,Plaznik A,Kostowski W,Bienkowski P

    更新日期:2006-09-30 00:00:00

  • Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder.

    abstract::In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxylase (DβH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We cond...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.pnpbp.2015.01.009

    authors: De La Garza R 2nd,Bubar MJ,Carbone CL,Moeller FG,Newton TF,Anastasio NC,Harper TA,Ware DL,Fuller MA,Holstein GJ,Jayroe JB,Bandak SI,Reiman KZ,Neale AC,Pickford LB,Cunningham KA

    更新日期:2015-06-03 00:00:00

  • Association study of serotonin 2A receptor (5-HT2A) and serotonin transporter (5-HTT) gene polymorphisms with schizophrenia.

    abstract:OBJECTIVE:To investigate (i) the association between four serotonergic polymorphisms (A-1438G and T102C of the 5-HT2A receptor gene, and 5-HTT VNTR and 5-HTTLPR of the 5-HT transporter gene) and schizophrenia and (ii) the potential interaction of those polymorphisms in the development of schizophrenia. SUBJECTS AND ME...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2007.01.012

    authors: Sáiz PA,García-Portilla MP,Arango C,Morales B,Alvarez V,Coto E,Fernández JM,Bascarán MT,Bousoño M,Bobes J

    更新日期:2007-04-13 00:00:00

  • Neurodevelopmental basis of bipolar disorder: a critical appraisal.

    abstract::Neurodevelopmental factors have been implicated in the pathophysiology of mental disorders. However, the evidence regarding their role in bipolar disorder is controversial. We reviewed the pertinent literature searching for evidence regarding a neurodevelopmental origin of bipolar disorder. Findings from clinical, epi...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章,评审

    doi:10.1016/j.pnpbp.2008.04.017

    authors: Sanches M,Keshavan MS,Brambilla P,Soares JC

    更新日期:2008-10-01 00:00:00

  • Protective role of Apelin-13 on amyloid β25-35-induced memory deficit; Involvement of autophagy and apoptosis process.

    abstract::Alzheimer's disease (AD) by progressive neurodegenerative pattern is associated with autophagy stress which is suggested as a potential cause of amyloid β (Aβ) aggregation and neural loss. Apelin-13, a neuropeptide with modulatory effect on autophagy, has been shown the beneficial effects on neural cell injuries. We i...

    journal_title:Progress in neuro-psychopharmacology & biological psychiatry

    pub_type: 杂志文章

    doi:10.1016/j.pnpbp.2018.10.005

    authors: Aminyavari S,Zahmatkesh M,Farahmandfar M,Khodagholi F,Dargahi L,Zarrindast MR

    更新日期:2019-03-08 00:00:00