Abstract：
:YM992, (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride, exhibited the biochemical profile of a selective serotonin (5-HT) reuptake inhibitor (SSRI) with 5-HT2A receptor antagonistic activity. YM922 showed the same high affinity as fluoxetine against the 5-HT reuptake site (Ki = 21 nM) and a similar affinity to that of crazodone against the 5-HT2A receptor (Ki = 86 nM). In other receptor binding studies, an affinity for the adrenergic alpha 1 receptor (Ki = 200 nM) and 5-HT2C receptor (Ki = 680 nM) was observed. In a monoamine uptake study, YM992 showed a selective 5-HT uptake inhibition (IC50 = 0.15 microM), but only very weakly inhibited both noradrenaline (NA) and dopamine (DA) uptake (IC50 = 3.1 microM (NA), > 10 microM (DA)). YM992 was also found to potently inhibit the aggregation of human platelets (IC50 = 1.9 microM), revealing antagonistic activity for the 5-HT2A receptor in vitro. Enhanced serotonergic neurotransmission, in particular that mediated by the 5-HT1A receptor, has recently been reported to be important in the long-term treatment of depressive disorders with antidepressants. In addition, some 5-HT1A receptor-mediated responses are known to be potentiated by co-administration of 5-HT2A receptor antagonists. Thus, YM992, having both selective 5-HT reuptake inhibition and 5-HT2A antagonistic activity, might show potent therapeutic activity as a novel antidepressant in comparison with conventional SSRIs.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Hatanaka K,Nomura T,Hidaka K,Takeuchi H,Yatsugi S,Fujii M,Yamaguchi Tdoi
10.1016/s0028-3908(96)00079-2subject
Has Abstractpub_date
1996-01-01 00:00:00pages
1621-6issue
11eissn
0028-3908issn
1873-7064pii
S0028390896000792journal_volume
35pub_type
杂志文章abstract：:The effects of chronic treatment with antidepressants on 5-HT-stimulated hydrolysis of phosphoinositide (PI) in the cerebral cortex of the guinea pig were examined. The pharmacological profile of the response was consistent with it being mediated by a 5-HT2 receptor. Chronic (but not acute) treatment with the selectiv...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90108-f
更新日期：1993-03-01 00:00:00
abstract：:Trazodone is one of the most commonly prescribed medicines for treating depression and insomnia. However, the pharmacological mechanism of action underlying trazodone's unique effects is unclear. Despite its nanomolar affinity for 5HT(2A) receptors, histamine(1) receptors and alpha(1) adrenoceptors the drug is given a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.05.011
更新日期：2007-08-01 00:00:00
abstract：:Dietary supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including a possible reduction in cognitive decline in the elderly. Here we report that pre-treatment with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) significantly reduced the survi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.02.003
更新日期：2008-05-01 00:00:00
abstract：:The uptake of norepinephrine into cortical punches from the brain of the rat was studied in the presence of buffer and plasma from patients containing bupropion and its metabolites. Even though bupropion and its metabolite (compound II) were equipotent in inhibiting the uptake of NE in buffer, compound II was twice as...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90041-9
更新日期：1986-02-01 00:00:00
abstract：:Stroke is one of the leading causes of death and serious disability in Westernized societies. The risk of stroke approximately doubles with each decade after the age of 55. Therefore, even though the incidence of stroke is declining, mostly because of the efforts to lower blood pressure and reduce smoking, the overall...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.08.022
更新日期：2018-07-01 00:00:00
abstract：:Clinical studies have shown that the major psychoactive ingredient of Cannabis sativa Δ9-tetrahydrocannabinol (THC) has some analgesic efficacy in neuropathic pain states. However, THC has a significant side effect profile. We examined whether the profile of THC could be improved by co-administering it with the first-...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.10.006
更新日期：2019-01-01 00:00:00
abstract：:The effect of neurotrophic factors on apoptosis induced by ionomycin, a potent Ca2+ ionophore, was investigated using cultured cortical neurons from embryonic rats. Brain-derived neurotophic factor (BDNF) and neurotrophin-3 (NT-3) prevented the ionomycin-mediated cell death in a dose-dependent manner. In contrast to t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00189-0
更新日期：1999-02-01 00:00:00
abstract：:An infusion of dopamine for 13 days into the nucleus accumbens of rat caused biphasic peaks of hyperactivity responding during infusion and an enhanced locomotor responsiveness to the dopamine agonist (-)N-n-propylnorapomorphine [(-)NPA] after the infusion when rats where initially preselected as low activity responde...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90073-5
更新日期：1985-03-01 00:00:00
abstract：:Glutamatergic neurotransmission in the central nucleus of the amygdala (CeA) plays an important role in many behaviors including anxiety, memory consolidation and cardiovascular responses. While these behaviors can be modulated by corticotropin releasing factor (CRF) and catecholamine signaling, the mechanism(s) by wh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.02.014
更新日期：2013-07-01 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：:Spinal metabotropic serotonin receptors encode transient experiences into long-lasting changes in motor behavior (i.e. motor plasticity). While interactions between serotonin receptor subtypes are known to regulate plasticity, the significance of molecular divergence in downstream G protein coupled receptor signaling ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.09.018
更新日期：2017-02-01 00:00:00
abstract：:The relevance and property of studies related to stress effects on immune function are undisputable. All studies conducted on stress-immune relationships, however, provide from physical and/or psychological stressors. Indeed, as far as it is of our knowledge brain-innate immune responses were not analyzed after anxiog...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.09.011
更新日期：2008-02-01 00:00:00
abstract：:Alcohol damages the developing brain and can lead to fetal alcohol syndrome. One of alcohol's most important neuropathologic effects is neuronal death. As neurons mature, they become less vulnerable to alcohol-induced death because they acquire a protective signaling pathway, mediated by nitric oxide (NO). This pathwa...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.12.006
更新日期：2009-03-01 00:00:00
abstract：:We investigated the possibility that pituitary adenylate cyclase activating peptide (PACAP) has a role in the control of contractility in the mouse ileum. PACAP-(1-27) produced tetrodotoxin (TTX)-insensitive, concentration-dependent reduction of the amplitude of the spontaneous contractions of longitudinal muscle up t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.09.011
更新日期：2004-03-01 00:00:00
abstract：:Suicide is a major global problem, claiming more than 800,000 lives annually. The neurobiological changes that underlie suicidal ideation and behavior are not fully understood. Suicidal patients have been shown to display elevated levels of inflammation both in the central nervous system and the peripheral blood. A gr...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2016.01.034
更新日期：2017-01-01 00:00:00
abstract：:Changes in brain reward and control systems of frontal cortical areas including the orbitofrontal cortex (OFC) are associated with alcohol use disorders (AUD). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, inclu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.04.019
更新日期：2018-07-15 00:00:00
abstract：:Regional differences are known in the serotonin-induced modulation of neuronal activity within the amygdala. This in vitro study in rats focuses on analyzing the ionic mechanism underlying serotonin-induced depolarization in the lateral amygdala. Serotonin depolarized membrane potential by 5 mV, which is underlain by ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.03.007
更新日期：2014-07-01 00:00:00
abstract：:Despite notable progress in recent decades, cigarette smoke persists as a leading cause of premature death and preventable disease. To weaken the link between nicotine reinforcement and the toxicity associated with combusted tobacco, the United States Food and Drug Administration is considering a product standard targ...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108200
更新日期：2020-09-15 00:00:00
abstract：:Adolescence is a critical period for postnatal brain maturation and a time during which there is increased susceptibility to developing emotional and cognitive-related disorders. Exercise during adulthood has been shown to increase hippocampal plasticity and enhance cognition. However, the impact of exercise initiated...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.05.007
更新日期：2019-02-01 00:00:00
abstract：:Central administration of corticotropin-like peptides generally blocks the analgesic action of opiate ligands, yet it is unclear whether this is due to an independent hyperalgesic action of corticotropin or to some other mechanism. Single cells in the ventromedial medulla of the anaesthetized rat were characterized as...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90130-4
更新日期：1987-12-01 00:00:00
abstract：:The effects of intracerebroventricular administration of morphine, the selective mu-agonist DAMGO, the delta-agonist DPDPE, the kappa-preferring peptide dynorphin A(1-13) and the kappa-agonist U50,488H on locomotor behaviour in the guinea pig were investigated. Morphine (total dose = 0.01, 0.1, 1, 10, 200 nmol), DAMGO...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90118-9
更新日期：1992-09-01 00:00:00
abstract：:To study the effects of maternal alcohol ingestion on brain adenylate cyclase in offspring, rats were given ethanol in the drinking water before, during and after gestation. Fifteen-day-old pups from alcoholic mothers had reduced body and wet brain weight and protein content with normal concentrations of DNA and RNA i...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90201-0
更新日期：1983-11-01 00:00:00
abstract：:This study examined the role of cannabinoid CB1 receptors (CB1r) in aggressive behavior. Social encounters took place in grouped and isolated mice lacking CB1r (CB1KO) and in wild-type (WT) littermates. Cognitive impulsivity was evaluated in the delayed reinforcement task (DRT). Gene expression analyses of monoaminoox...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.07.013
更新日期：2013-12-01 00:00:00
abstract：:Histamine H3 receptor (H3R) antagonists are currently being investigated for the possible therapeutic use in various cognitive deficits such as those in schizophrenia, attention deficit hyperactivity disorder and Alzheimer's disease. Our previous studies suggest a role for H3Rs in ethanol-related behaviors in rat and ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.10.027
更新日期：2011-06-01 00:00:00
abstract：:While the activity-dependent mechanisms guiding functional maturation of synaptic transmission postsynaptically are well characterized, less is known about the corresponding presynaptic mechanisms. Here we show that during the first postnatal week, a subset of CA3-CA1 synapses express postsynaptically induced LTP that...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.11.019
更新日期：2013-04-01 00:00:00
abstract：:GABA(B) receptors inhibit and dopamine D1 receptors stimulate the release of GABA from striatal terminals in the pars reticulata of the substantia nigra. Here we have studied the interaction between both classes of receptors by exploring the effect of GABA(B) receptors upon the stimulation of depolarization-induced [(...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.07.014
更新日期：2007-10-01 00:00:00
abstract：:High concentrations of diazepam-binding inhibitor (DBI) mRNA have been detected in astrocytoma, suggesting that DBI-derived peptides may play a role in glial cell proliferation. In the present study, we have investigated the effect of a processing product of DBI, the octadecaneuropeptide ODN, on DNA synthesis in cultu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00231-7
更新日期：1999-05-01 00:00:00
abstract：:We investigated block of voltage-dependent Ca channels in freshly dissociated rat central and peripheral neurons by the synthetic peptide omega-Aga-IVA. Synthetic omega-Aga-IVA blocked approximately 90% of the high-threshold Ca current in cerebellar Purkinje neurons with an estimated Kd of approximately 1.5 nM, slight...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90010-z
更新日期：1993-11-01 00:00:00
abstract：:Behavioral and electrophysiological comparative analyses of the effects of 2-o-chlorobenzoyl-4-chloro-N-methyl-N alpha-glycylglycinanilide hydrate (45-0088-S) and diazepam on the CNS were performed with cats and monkeys. No essential difference between 45-0088-S and diazepam on the effects in the CNS was observed, alt...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90024-7
更新日期：1982-05-01 00:00:00
abstract：:Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90077-o
更新日期：1991-06-01 00:00:00
