Abstract:
:The hypothesis that aberrant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activity contributes to epileptogenesis and neurodegeneration has prompted the search for AMPA receptor antagonists as potential therapeutics to treat these conditions. We describe the functional characterization of a novel quinazolin-4-one AMPA receptor antagonist, 3-(2-chloro-phenyl)-2-[2-(6-diethylaminomethyl-pyridin-2-yl)-vinyl]-6-fluoro-3H-quinazolin-4-one (CP-465,022). This compound inhibits AMPA receptor-mediated currents in rat cortical neurons with an IC(50) of 25 nM. Inhibition is noncompetitive with agonist concentration and is not use- or voltage-dependent. CP-465,022 is selective for AMPA over kainate and N-methyl-D-aspartate receptors. However, the compound is found to be equipotent for AMPA receptors composed of different AMPA receptor subunit combinations. This is indicated by the finding that CP-465,022 is equivalently potent for inhibition of AMPA receptor-mediated responses in different types of neurons that express different AMPA receptor subunits. Thus, CP-465,022 provides a new tool to investigate the role of AMPA receptors in physiological and pathophysiological processes.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Lazzaro JT,Paternain AV,Lerma J,Chenard BL,Ewing FE,Huang J,Welch WM,Ganong AH,Menniti FSdoi
10.1016/s0028-3908(01)00170-8subject
Has Abstractpub_date
2002-02-01 00:00:00pages
143-53issue
2eissn
0028-3908issn
1873-7064pii
S0028390801001708journal_volume
42pub_type
杂志文章abstract::Inhibition of calcium-evoked [3H]ACh release by different classes of calcium channel blockers was compared among calcium-naive synaptosomes from chick, frog and rat forebrain tissues. In all three species, [3H]ACh release was insensitive to nifedipine (0.03-3 microM) but was completely inhibited by cadmium (IC50 range...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90181-n
更新日期:1992-03-01 00:00:00
abstract::The posterior hypothalamic receptors involved in the cardiovascular responses to electrical stimulation of the rostral ventrolateral medulla were investigated in urethane-anaesthetized rats. Electrical stimulation of the rostral ventrolateral medulla produced a significant increase in systolic blood pressure. This res...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90183-c
更新日期:1991-07-01 00:00:00
abstract::This study shows that the selective GABAB antagonist CGP 35348 had no effect on body temperature in mice in doses up to 300 mg/kg i.p. However, the highest dose abolished the hypothermia induced by the GABAB agonist baclofen (10 mg/kg i.p.) but not that produced by the GABA-mimetic progabide (200 mg/kg i.p.); the benz...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90018-7
更新日期:1991-05-01 00:00:00
abstract::Electrophysiological studies suggest that 5-HT autoreceptor desensitization may be responsible for the delayed clinical efficacy of some antidepressant drugs, such as selective 5-HT reuptake inhibitors (SSRI) and certain MAO inhibitors (MAOI). In the present study we have used in vivo microdialysis to test this hypoth...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)90062-0
更新日期:1994-03-01 00:00:00
abstract::It has been shown that endogenous adenosine 5'-triphosphate (ATP) as well as its exogenously applied structural analogue, 2-methylthio ATP (2-MeSATP), facilitate the release of dopamine from axon terminals in the rat nucleus accumbens (NAc) by activating ATP-sensitive P2 receptors. In the present study, reversed micro...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00033-8
更新日期:2001-06-01 00:00:00
abstract::The influence of naloxone (a narcotic antagonist), bicuculline (a GABA antagonist), phentolamine (an alpha-blocking agent), propranolol (a beta-adrenergic blocking agent), haloperidol (a dopaminergic blocking agent), methysergide (a serotonergic blocking agent) and atropine (a muscarinic blocking agent), on the antino...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(84)90143-6
更新日期:1984-06-01 00:00:00
abstract::The present review gives an overview of current pharmacological treatment options of tic disorders and Tourette Syndrome (TS). After a short summary on phenomenology, clinical course and comorbid conditions we review indications for pharmacological treatment in detail. Unfortunately, standardized and large enough drug...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2012.05.043
更新日期:2013-05-01 00:00:00
abstract::Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through wh...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.08.033
更新日期:2019-01-01 00:00:00
abstract::We describe a touchscreen method that satisfies a proposed 'wish-list' of desirables for a cognitive testing method for assessing rodent models of schizophrenia. A number of tests relevant to schizophrenia research are described which are currently being developed and validated using this method. These tests can be us...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2011.04.011
更新日期:2012-03-01 00:00:00
abstract::An important feature of cocaine addiction in humans is the emergence of negative affect (e.g., dysphoria, irritability, anhedonia), postulated to play a key role in craving and relapse. Indeed, the DSM-IV recognizes that social, occupational and/or recreational activities become reduced as a consequence of repeated dr...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2013.04.025
更新日期:2014-01-01 00:00:00
abstract::The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90171-k
更新日期:1992-03-01 00:00:00
abstract::Diazepam binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Levels of DBI in cerebrospinal fluid (CSF) were found to be elevated in depressed patients, when compared to age- and sex-matched normal controls. Levels of the peptide, corticotropin-releasing hormone (...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(11)80014-6
更新日期:1991-12-01 00:00:00
abstract::Recent observations from synaptosome preparations have questioned the tetrodotoxin (TTX) insensitivity of nicotine-evoked release in the striatum, a characteristic previously considered diagnostic of presynaptically located nicotinic acetylcholine receptors (nAChRs). Therefore, we have undertaken a comparison of nicot...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(96)00117-7
更新日期:1996-01-01 00:00:00
abstract::The neurochemical basis for the clinical observation that some patients receiving a large dose of haloperidol exhibit no extrapyramidal side effects was investigated in rats. Haloperidol at doses of 1, 2.5, 5, 7.5 and 10 mg/kg (i.p.) caused a dose-dependent decrease in the duration of catalepsy. Haloperidol at a dose ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90079-6
更新日期:1985-03-01 00:00:00
abstract::Ethylcholine mustard aziridinium ion (AF64A), or vehicle, was infused bilaterally (3 nmol/3 microliter per side) into the lateral ventricles of rats. The effect of such treatment on various cholinergic responses was measured in the hippocampus, cortex and striatum. Potassium-stimulated release of acetylcholine from su...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90031-0
更新日期:1985-05-01 00:00:00
abstract::The effects of chronic treatment with haloperidol on [3H]PK 11195 binding and labelling of the peripheral-type benzodiazepine receptor (PBR) in the rat brain and peripheral tissues were investigated using an in vitro receptor binding technique. The intraperitoneal injection with haloperidol (0.3 or 1.0 mg/kg) for 21 d...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(96)00040-8
更新日期:1996-01-01 00:00:00
abstract::In this study, the role of CB₂r on aversive memory consolidation was further evaluated. Mice lacking CB₂r (CB2KO) and their corresponding littermates (WT) were exposed to the step-down inhibitory avoidance test (SDIA). MAP2, NF200 and synaptophysin (SYN)-immunoreactive fibers were studied in the hippocampus (HIP) of b...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.05.034
更新日期:2013-10-01 00:00:00
abstract::Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Here...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.01.024
更新日期:2017-05-01 00:00:00
abstract::Increasingly in the realm of neurological disorders, particularly those involving neurodegeneration, mitochondrial dysfunction is emerging at the core of their pathogenic processes. Most of these diseases still lack effective treatment and are hampered by a shortfall in the development of novel medicines. Clearly new ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2015.10.033
更新日期:2016-03-01 00:00:00
abstract::The 15q25 gene cluster contains genes that code for the α5, α3, and β4 nicotinic acetylcholine receptor (nAChRs) subunits, and in human genetic studies, has shown the most robust association with smoking behavior and nicotine dependence to date. The limited available animal studies implicate a role for the α5 and β4 n...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.01.017
更新日期:2013-07-01 00:00:00
abstract::Metabotropic glutamate (mGlu) receptors are implicated in many neurological and psychiatric diseases and are the targets of therapeutic agents currently in clinical development. Their activation has diverse effects in the central nervous system (CNS) that includes an involvement in synaptic plasticity. We previously r...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.03.011
更新日期:2013-11-01 00:00:00
abstract::The preparation of an isolated hemisected spinal cord preparation, maintained in vitro, from mature (180-300 g body weight) rats is described. Sacral and coccygeal segments (S2-Co1) gave consistent ventral root reflexes (DR-VRP) from electrical stimulation of dorsal roots. The mean latency and amplitude of the fastest...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90138-4
更新日期:1988-05-01 00:00:00
abstract::Recently it has been reported that "I(f) channel blockers", which block the hyperpolarization-activated inward current (I(f)) in heart sino atrial node cells, also block the hyperpolarization-activated inward current (I(h)) in other tissues. Here we compared the effects of one of these agents, ZD7288 [4-(N-ethyl-N-phe...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(99)00207-5
更新日期:2000-04-27 00:00:00
abstract::The effects of 5-hydroxytryptamine (5-HT) on neuronal excitability, evaluated as depolarization-induced firing rate, and on amino acid release, measured as electrically-evoked [(3)H]GABA and [(3)H]d-aspartate efflux, were investigated in rat primary cortical neuronal cultures. 5-HT displayed a concentration-dependent,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.017
更新日期:2007-03-01 00:00:00
abstract::Due in part to their rich behavioral repertoire rats have been widely used in behavioral studies of drug abuse-related traits for decades. However, the mouse became the model of choice for researchers exploring the genetic underpinnings of addiction after the first mouse study was published demonstrating the capabilit...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.05.047
更新日期:2014-01-01 00:00:00
abstract::BU99006 is an irreversible I(2) ligand which selectively inactivates I(2) binding sites, making it an ideal tool with which to study I(2) site mechanism. We sought to determine the effects of BU99006 on I(2) binding in relation to monoamine oxidase (MAO), and the time course of these effects. In vitro, rat brain membr...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.08.010
更新日期:2007-02-01 00:00:00
abstract::Visual cues that become associated with the consumption of psychostimulant drugs energize craving and the intake of the drug by mechanisms of which little is known. In two experiments using in vivo microdialysis in freely moving rats we compared the effects of visual and auditory stimulation with that of cocaine (0, 5...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.002
更新日期:2007-03-01 00:00:00
abstract::Toll-like receptors (TLRs) are the sensors of pathogen-associated molecules that trigger tailored innate immune intracellular signalling responses to initiate innate immune reactions. Data from the experimental autoimmune encephalomyelitis (EAE) model indicates that TLR signalling machinery is a pivotal player in the ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2016.04.009
更新日期:2017-02-01 00:00:00
abstract::Application of capsaicin (CAP), bradykinin (BK) or nicotine (NIC) to intraluminally perfused rat tracheas induced an increase in calcitonin gene-related peptide (CGRP) levels in the perfusates. Depletion of sensory afferent CGRP with systemic CAP pretreatment resulted in a significant reduction of CGRP release evoked ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(05)80004-8
更新日期:1994-10-01 00:00:00
abstract::A once daily injection to rats of triiodothyronine (T3; 100 micrograms/kg s.c.) for 10 days enhanced the locomotor responses of rats pretreated with tranylcypromine (5 mg/kg) to an injection into the nucleus accumbens of dopamine (5 micrograms bilaterally), when tested 24 hr after the last T3 administration. This trea...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90156-3
更新日期:1982-02-01 00:00:00