Abstract：
:Metabotropic glutamate mGlu(1) receptors play a modulatory role in the nervous system. They enhance cell excitability, modulate synaptic neurotransmission and are involved in synaptic plasticity. During the last 10 years, several selective metabotropic glutamate mGlu(1) receptor competitive antagonists and potentiators have been discovered. These pharmacological tools, together with early and later work in metabotropic glutamate mGlu(1) receptor mutant mice have allowed studying the role of the receptor in various aspects of psychiatric illnesses such as anxiety, depression and schizophrenia. We here review the data on selective metabotropic glutamate mGlu(1) receptor antagonists in support of their potential as anxiolytic and antidepressant treatments. We propose a rationale for the development of metabotropic glutamate mGlu(1) receptor positive allosteric modulators for the treatment of schizophrenia. Potential side effects of blockade and activation of metabotropic glutamate mGlu(1) receptors are addressed, with special focus on the differential effects of metabotropic glutamate mGlu(1) receptor antagonists in cognition models with positive reinforcement versus those that use aversive learning procedures. Further development of negative allosteric modulators and more drug-like positive allosteric modulators will be required in order to decipher the therapeutic efficacy and safety margin of these compounds in the clinic.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lesage A,Steckler Tdoi
10.1016/j.ejphar.2009.12.043subject
Has Abstractpub_date
2010-08-10 00:00:00pages
2-16issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(10)00258-Xjournal_volume
639pub_type
杂志文章,评审abstract：:The benzodiazepine drugs modulate gamma-aminobutyric acid (GABA)-mediated synaptic transmission via a high-affinity binding site that is part of the GABA(A) receptor complex, but which is distinct from the GABA binding site. Ro15-4513 is a benzodiazepine negative modulator of GABA action that displays unique anti-etha...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(90)90199-8
更新日期：1990-06-12 00:00:00
abstract：:We determined the role of high-grade inflammation on endothelial function and its association with biomarkers of endothelial dysfunction in collagen-induced arthritis. Sprague-Dawley rats were divided into a control (n = 12) or collagen-induced arthritis (CIA; n = 21) group. To induce arthritis, Bovine-type-II collage...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172786
更新日期：2019-12-15 00:00:00
abstract：:Endogenous inhibitory controls were studied in the spinal nerve ligation model of neuropathic pain. Atipamezole, a selective alpha2-adrenoceptor antagonist, produced both mechanical and cold allodynia in those rats which had not developed clear neuropathic symptoms. The same doses (50 microg i.t. or 1 mg/kg s.c.) did ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00910-8
更新日期：1999-01-29 00:00:00
abstract：:The activation of C-fibers in the airways induces coughing, mucus production and bronchoconstriction, which are also symptoms of airway diseases. In this study, we evaluated the role of the C-fibers and the TRPV1 (transient receptor potential vanilloid 1) receptor in an experimental mouse model of allergic airway infl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.04.027
更新日期：2011-07-15 00:00:00
abstract：:In rat stomach fundus, contractions induced by Ca2+ (1.8 mM) were strikingly potentiated by thapsigargin. This potentiation was partially inhibited by the blockers of Ca2+ release activated channels (CRACs), miconazole and SK&F96365 ([1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole, HCL]) and sli...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01537-9
更新日期：1998-01-19 00:00:00
abstract：:The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenze...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01592-3
更新日期：2002-05-17 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01014-7
更新日期：2001-06-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.05.045
更新日期：2004-08-02 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00593-6
更新日期：1996-11-07 00:00:00
abstract：:The effects of Ca2+ channel antagonists on the capsaicin-induced cough reflex in guinea pigs were studied. Intraperitoneal injection of nifedipine, verapamil and flunarizine in doses that ranged from 0.3 to 3.0 mg/kg decreased the number of coughs in a dose-dependent manner. These Ca2+ channel antagonists exhibited an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90072-c
更新日期：1992-02-25 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.02.013
更新日期：2017-03-15 00:00:00
abstract：:We investigated in vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone from Saussurea lappa, on tumor necrosis factor (TNF)-alpha and nitric oxide (NO) release, and lymphocyte proliferation. Cynaropicrin strongly inhibited TNF-alpha release from lipopolysaccharide-stimulated murine macrophage, RAW...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00337-x
更新日期：2000-06-23 00:00:00
abstract：:Evidence has shown that downstream signaling by mu opioid receptor (MOR) agonists that recruit β-arrestin2 may lead to the development of tolerance. Also, it has been suggested that opioid receptor desensitization and cyclic AMP overshoot contributes to the development of tolerance and occurrence of withdrawal, respec...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.03.013
更新日期：2018-05-15 00:00:00
abstract：:Although cannabinoids are known to be more effective analgesics against chronic rather than acute pain, the mechanism underlying this phenomenon is still unclear. We report now that contralateral thalamic cannabinoid CB(1) receptors are upregulated after unilateral axotomy of the tibial branch of the sciatic nerve, a ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00798-1
更新日期：2001-03-09 00:00:00
abstract：:In the present study, the effects of dopamine receptor agonists and antagonists on naloxone-induced jumping in morphine-dependent mice were examined. Mice were rendered dependent as described in the methods section. Naloxone was injected to elicit jumping (as withdrawal sign). The first group received dopamine recepto...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02149-0
更新日期：2002-09-20 00:00:00
abstract：:We have characterized a specific binding site for angiotensin IV on bovine aortic endothelial cell membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.71; average of two experiments that yielded values of 0.71 and 0.72 n...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90142-6
更新日期：1995-10-15 00:00:00
abstract：:Phenoxybenzamine greatly attenuated phenylephrine-induced contractions of dog saphenous vein in vitro, but had less effect on contractions induced by clonidine. The phenoxybenzamine-resistant responses to clonidine were not affected by prazosin or by corynanthine but were competitively antagonized by yohimbine (pA2 8....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90219-9
更新日期：1982-12-03 00:00:00
abstract：:The ability of the human interleukin-1 receptor antagonist, IL-1ra, to inhibit aerosolized antigen-induced airway hyperreactivity to i.v. substance P and bronchoalveolar lavage inflammatory cell accumulation, under in vivo conditions, was assessed in guinea pigs. Pretreatment with IL-1ra (30 mg/kg i.p., administered 3...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90621-a
更新日期：1992-03-31 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.08.028
更新日期：2009-10-25 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.03.006
更新日期：2016-04-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2018.06.029
更新日期：2018-08-15 00:00:00
abstract：:Inhibitors of phosphodiesterases 3 and 4, the main cyclic AMP (cAMP) degrading enzymes in arteries, may have therapeutic potential in cerebrovascular disorders. We analysed the effects of such phosphodiesterases in guinea pig cerebral arteries with organ bath technique and cyclic nucleotide assays. Guinea pig and huma...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.02.038
更新日期：2004-04-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(92)90073-5
更新日期：1992-07-01 00:00:00
abstract：:The cerebellum receives indolaminergic fibers influencing Purkinje cell discharges. Data from our laboratories have demonstrated an endogenous release of serotonin (5-HT) and a Na(+)-dependent uptake and Ca(2+)-dependent release of [3H]5-HT from slices, homogenates and synaptosomal fractions of the rat cerebellar mole...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90555-5
更新日期：1991-05-30 00:00:00
abstract：:In the spinal cord of the pentobarbitone-anaesthetised cat, microelectrophoretic pitrazepin reduced the inhibitory effects on neuronal firing of both glycine and GABA. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90590-x
更新日期：1986-11-19 00:00:00
abstract：:T-type Ca(2+) currents were recorded in 2 mM Ca(2+) from HEK293 cells stably expressing the low voltage-activated Ca(2+) channel sub-unit alpha(1I). These currents were inhibited by the known Ca(2+) channel antagonist mibefradil with an IC(50) close to 1 microM. SB-209712 (1,6,bis¿1-[4-(3-phenylpropyl)piperidinyl]¿hex...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00740-8
更新日期：2000-10-27 00:00:00
abstract：:The influence of degradation by peptidases on concentration-response relationships for peptide agonists of the tachykinin and bombesin-like families was investigated. The combined presence of three peptidase inhibitors, phosphoramidon (1 microM), captopril (1 microM) and bestatin (100 microM), had no significant effec...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90520-g
更新日期：1990-02-06 00:00:00
abstract：:Several studies have shown that glycine transporter 1 (GlyT1) inhibitors have anxiolytic actions. There are two types of glycine receptor: the strychnine-sensitive glycine receptor (GlyA) and the strychnine-insensitive glycine receptor (GlyB); however, which receptor is the main contributor to the anxiolytic actions o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.11.024
更新日期：2015-01-05 00:00:00
abstract：:The effect of DL-propranolol on NO release in perfused rat hindquarters was studied by using oxyhemoglobin as a capture system to allow the quantitative assay of NO production. In some experiments the stable prostacyclin metabolite 6-keto-PGF1 alpha (6-keto) was simultaneously assayed. We observed that: (1) DL-propran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90686-x
更新日期：1992-03-24 00:00:00
abstract：:Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.07.029
更新日期：2010-10-25 00:00:00
