Abstract:
:Improgan is a chemical congener of the H2 antagonist cimetidine which shows the profile of a highly effective analgesic when administered directly into the CNS. Although the improgan receptor is unknown, improgan activates analgesic pathways which are independent of opioids, but may utilize cannabinoid mechanisms. To discover selective, potent, improgan-like drugs, seven compounds chemically related to improgan were synthesized and tested for antinociceptive activity in rats after intracerebroventricular (icv) administration. Among a series of improgan congeners in which the alkyl chain length of improgan ((-CH2)3-) was varied, five compounds showed full agonist antinociceptive activity with potencies greater than that of improgan. VUF5420 (containing (-CH2)4-, EC50 = 86.1 nmol) produced maximal antinociceptive activity after doses which showed no motor impairment or other obvious toxicity, and was 2.3-fold more potent than improgan (EC50 = 199.5 nmol). As found previously with improgan, VUF5420-induced antinociception was unaffected by administration of the opioid antagonist naltrexone, but was inhibited by the CB1 antagonist SR141716A, suggesting a non-opioid, cannabinoid-related analgesic action. However, VUF5420 showed very low affinity (Kd approximately 10 microM) on CB1-receptor activation of 35S-GTPgammaS binding, indicating that this drug does not directly interact with the CB1 receptor in vivo. The present results show that VUF5420 is a high potency, improgan-like, non-opioid analgesic which may indirectly activate cannabinoid pain-relieving mechanisms.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Hough LB,de Esch IJ,Janssen E,Phillips J,Svokos K,Kern B,Trachler J,Abood ME,Leurs R,Nalwalk JWdoi
10.1016/j.neuropharm.2006.04.003subject
Has Abstractpub_date
2006-09-01 00:00:00pages
447-56issue
3eissn
0028-3908issn
1873-7064pii
S0028-3908(06)00094-3journal_volume
51pub_type
杂志文章abstract::Anxiety and depression are considered as stress-related disorders, which present considerable sex differentiation. In animal models of anxiety and depression sex differences have been described and linked to the sexually dimorphic hypothalamus-pituitary-adrenals (HPA) axis. The present study aimed to adjust corticoste...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.08.025
更新日期:2012-01-01 00:00:00
abstract::Selegiline is an irreversible inhibitor of monoamine oxidase B with trophic and neuroprotective effects. Because of evidence for decreased dopaminergic function during the withdrawal syndromes associated with opiates and other medications with potential for abuse, we investigated effects of treatment with selegiline o...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00093-8
更新日期:1998-08-01 00:00:00
abstract::The patterns of spontaneous firing recorded from 25 cells in slice preparations of rat cerebral cortex were characterised using inter-spike interval plots (ISI). Histograms of the ISI showed two peaks having modal values of 20 and 82ms, corresponding to episodes of high frequency bursts of action potentials, and a low...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90062-0
更新日期:1985-06-01 00:00:00
abstract::Extracts of the skin of Pseudophryne coriacea displayed a powerful stimulant action on the leech helical muscle, both in vitro and in vivo. In the isolated dorsal muscle, the extract caused the appearance of vigorous phasic movements, accompanied by rapid increase in tonus, up to intense spasm. Hyoscine, physostigmine...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90001-8
更新日期:1986-08-01 00:00:00
abstract::Angiotensin IV (Val(1)-Tyr(2)-Ile(3)-His(4)-Pro(5)-Phe(6)) has demonstrated potential cognitive-enhancing effects. The present investigation assessed and characterized: (1) dose-dependency of angiotensin IV's cognitive enhancement in a C57BL/6J mouse model of novel object recognition, (2) the time-course for these eff...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.01.025
更新日期:2013-07-01 00:00:00
abstract::The aim of the present study was to investigate if different levels of circulating corticosterone (CORT) modulate the effect of nicotine on prepulse inhibition (PPI), a measure of sensorimotor gating that is disrupted in schizophrenia and other mental illnesses. Four groups of mice were investigated: sham-operated, ad...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.08.015
更新日期:2005-01-01 00:00:00
abstract::This review will provide an overview of the non-drug based approaches that have been demonstrated to enhance cognitive function of the compromised brain, primarily focussed on the two most widely adopted paradigms of environmental enrichment and enhanced physical exercise. Environmental enrichment involves the generat...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2012.06.029
更新日期:2013-01-01 00:00:00
abstract::Pyrethroids, widely used insecticides with low acute toxicity in mammals, affect sodium channels in neurons. In a primary culture of rat cortical neurons, deltamethrin (DM), a type II pyrethroid, markedly enhanced the expression of brain-derived neurotrophic factor (BDNF) exon IV-IX (Bdnf eIV-IX) mRNA. In this study, ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.10.023
更新日期:2012-02-01 00:00:00
abstract::Cocaine induces neuroinflammatory response and interleukin-1 beta (IL1β) is suggested a final effector for many cocaine-induced inflammatory signals. Recently, the chemokine fractalkine (CX3CL1) has been reported to regulate hippocampus-dependent neuroinflammation and synaptic plasticity via CX3C-receptor 1 (CX3CR1), ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2019.107840
更新日期:2020-01-01 00:00:00
abstract::The present study investigated the effects of WB4101, a selective alpha 1-adrenoceptor blocking agent, and idazoxan, a selective alpha 2-adrenoceptor blocking agent, on antinociception and sedation in the rat mediated by adrenoceptors. Selective alpha 1-adrenoceptor agonists, e.g. ST587 and methoxamine induced antinoc...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90234-0
更新日期:1986-04-01 00:00:00
abstract::The N-methyl-D-aspartate (NMDA) antagonist ifenprodil and several structurally related compounds are highly selective for the NR2B-containing receptor subtype. This selectivity could provide an explanation for the reported difference of the analgesic and side-effect profile of ifenprodil-like compounds from other NMDA...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00148-9
更新日期:2001-01-01 00:00:00
abstract::Allopregnanolone (ALLO), a potent positive-allosteric modulator of the action of GABA at GABA(A) receptors, is synthesized in the brain from progesterone by the sequential action of two enzymes: 5alpha-reductase and 3alpha-hydroxysteroidoxidoreductase. The concentration of ALLO in various parts of the mouse brain vari...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(99)00149-5
更新日期:2000-01-28 00:00:00
abstract::In nonhuman primates, anxiety levels are typically assessed by observing social hierarchies or behavior in an intruder task. As measures of anxiety might influence performance on a particular cognitive task, it is important to analyze these measures in the same room as used for the cognitive task. As we use a playroom...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.08.014
更新日期:2012-01-01 00:00:00
abstract::The ventral part of the medial prefrontal cortex (mPFC) plays an important role in mood and cognition. This study examined the effect of the 5-HT in this region by measuring the electrophysiological response of ventral mPFC neurones to electrical stimulation of the dorsal and median raphe nuclei (DRN and MRN), which a...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00139-4
更新日期:2003-07-01 00:00:00
abstract::The present study used pharmacological and gene ablation techniques to examine the involvement of kappa opioid receptors (KOPr) in modulating the convulsant effects of two mechanistically different drugs: cocaine and pentylenetetrazol (PTZ; GABA-A receptor antagonist) in mice. Systemic administration of the selective ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.10.007
更新日期:2007-03-01 00:00:00
abstract::Nitric oxide synthase (NOS) enzyme activity was determined in a comprehensive selection of regions of the rat brain. The effects of lateral ventricular administration of N omega-nitro-L-arginine (L-NA, 30 micrograms) and its methyl ester (L-NAME, 3-100 micrograms) on NOS activity were examined in the ipsilateral and c...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(95)00036-6
更新日期:1995-06-01 00:00:00
abstract::The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and p...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90160-8
更新日期:1988-02-01 00:00:00
abstract::The identification of a second 5-HT(3) (5-HT(3B)) subunit provides an explanation for 5-HT(3) receptor heterogeneity. We investigated whether introduction of recombinant 5-HT(3B) subunits would alter the functional properties of mouse neuroblastoma 5-HT(3) receptors. RT-PCR analysis revealed that NB41A3 cells contain ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00376-3
更新日期:2003-02-01 00:00:00
abstract::Long-term L-DOPA treatment for Parkinson's disease (PD) is limited by motor complications, particularly L-DOPA-induced dyskinesia (LID). A therapy with the ability to ameliorate LID without reducing anti-parkinsonian benefit would be of great value. We assessed the ability of TC-8831, an agonist at nicotinic acetylcho...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.06.005
更新日期:2013-10-01 00:00:00
abstract::The homotrimeric P2X3 subtype, one of the seven members of the ATP-gated P2X receptor family, plays a role in sensory neurotransmission, including nociception. To overcome the bias resulting from fast desensitization of the P2X3 receptor in dose-response analyses, a non-desensitizing P2X2-X3 receptor chimera has been ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.01.010
更新日期:2014-04-01 00:00:00
abstract::mGlu7 receptors are coupled to Gi/Go-proteins and activate multiple transduction pathways, including inhibition of adenylyl cyclase activity and stimulation of ERK1/2 and JNK pathways. mGlu7 receptors play an important role in cognition and emotion and are involved in stress-related disorders such as anxiety and depre...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.10.013
更新日期:2014-02-01 00:00:00
abstract::Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD fo...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.12.017
更新日期:2016-04-01 00:00:00
abstract::Ketoprofen is a non-steroidal antiinflammatory drug (NSAID) which provides effective analgesia in situations of pain provoked by tissue inflammation. However, the location of its analgesic effects, (peripheral tissues versus central nervous system), have not been clearly identified and separated. In the present study ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00120-2
更新日期:1997-10-01 00:00:00
abstract::There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the dist...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(95)00155-7
更新日期:1996-01-01 00:00:00
abstract::Electrophysiology, immunostaining and time lapse imaging techniques were employed to study the mechanism of long-term depression (LTD) induced by DHPG, a specific group I metabotropic glutamate receptor (mGluR) agonist. Experiments were performed in primary hippocampal culture or in the CA1 area of acute rat hippocamp...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00134-4
更新日期:2001-11-01 00:00:00
abstract::1-Methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) causes long-term depletions in cortical and hippocampal serotonin (5-HT) and norepinephrine (NE) that are accompanied by acute elevations in glial fibrillary acidic protein (GFAP) and argyrophilia. To further investigate the hypothesis that these cha...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.09.006
更新日期:2006-03-01 00:00:00
abstract::Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1AR) in the brainstem, a major wake/REM sleep regulatory center. However, the...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.06.014
更新日期:2018-08-01 00:00:00
abstract::In the human genome, 22 genes are coding for the class C G protein-coupled receptors that are receptors for the two main neurotransmitters glutamate and γ-aminobutyric acid, for Ca(2+) and for sweet and amino acid taste compounds. In addition to the GPCR heptahelical transmembrane domain responsible for G-protein acti...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2010.08.009
更新日期:2011-01-01 00:00:00
abstract::Alternative splicing of the dopamine D2 receptor gene produces two distinct isoforms referred to as D2long (D2L) and D2short (D2S). In mesencephalic dopamine neurons, inhibition of the firing rate through activation of somatodendritic D2 receptors and blockade of neurotransmitter release through stimulation of termina...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.11.010
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVES:Recombinant tissue plasminogen activator (rtPA) is widely used for patients with thromboembolic disease, and increasing evidence indicates that it can directly induce neurotoxicity independent of its thrombolysis property. Here, we aimed to confirm the long-term effect of rtPA on animal's behavior, and inves...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.09.039
更新日期:2018-01-01 00:00:00