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 at high doses to achieve clinical efficacy suggesting that other target activities may also contribute to its effects. Here we report that trazodone inhibits recombinant T-type calcium channels (Ca(v)3.1, Ca(v)3.2 and Ca(v)3.3) in whole-cell patch-clamp studies at therapeutically relevant concentrations (IC(50)=43 microM, 45 microM, 23 microM, respectively). Inhibition was not use-dependent and showed only moderate voltage-dependence. Tonic block of Ca(v)3.1 channels held at negative membrane potentials suggested drug interaction with channels in the resting state. The major metabolite of trazodone, m-chlorophenylpiperazine, showed comparable potency on Ca(v)3.3 channels (IC(50)=35 microM) and was less active on Ca(v)3.1 channels (IC(50)=317 microM). We also demonstrate trazodone's inhibitory effects on native T-type calcium currents recorded from subthalamic neurons in a patch-clamp rat brain slice assay (approximately 30% inhibition at 100 microM). Our data suggest that T-type calcium channel antagonism may contribute to the pharmacology of trazodone and its reported neurological effects.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Kraus RL,Li Y,Jovanovska A,Renger JJdoi
10.1016/j.neuropharm.2007.05.011subject
Has Abstractpub_date
2007-08-01 00:00:00pages
308-17issue
2eissn
0028-3908issn
1873-7064pii
S0028-3908(07)00149-9journal_volume
53pub_type
杂志文章abstract：:Maternal sleep deprivation (MSD) has been suggested to be associated with increased frequency of neurodevelopmental disorders in offspring in both humans and animal models. However, the underlying cellular and molecular mechanism is still unclear. We have recently reported that MSD at different stages of pregnancy imp...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.01.030
更新日期：2018-05-01 00:00:00
abstract：:Heterogeneous binding interactions of cerebellar GABA(A) receptors were investigated with GABA agonists and neurosteroids. GABA(A) receptors of rat cerebellum were labelled with [(3)H]ethynylbicycloorthobenzoate (EBOB), a convulsant radioligand. Saturation analysis revealed a homogenous, nanomolar population of [(3)H]...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.04.003
更新日期：2005-09-01 00:00:00
abstract：:For a number of years it has been known that the CNS convulsant picrotoxin inhibits the GABA(A) receptor, an anion-selective member of the ligand-gated ion channel (LGIC) superfamily. PTX also inhibits other anion-selective LGIC members, such as GABA(C), glycine and glutamate-gated Cl(-) channels. In the present repor...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00032-7
更新日期：2003-03-01 00:00:00
abstract：:In this study, we evaluated the gastric effects of methylnaltrexone, an opioid receptor antagonist that does not cross the blood-brain barrier in vivo, on mu, kappa and delta opioid agonists induced brainstem unitary responses in an in vitro neonatal rat brainstem-gastric preparation. Single units in the medial subnuc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00192-0
更新日期：1999-03-01 00:00:00
abstract：:Schizophrenia is associated with increased oxidative stress, although the source of this redox disequilibrium requires further study. Altered tryptophan metabolism has been described in schizophrenia, possibly linked to inflammation and glutamate-directed excitotoxicity. Social isolation rearing (SIR) in rats induces ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.02.021
更新日期：2012-06-01 00:00:00
abstract：:Behavioral sensitization, or augmented locomotor response to successive drug exposures, results from neuroadaptive changes contributing to addiction. Both the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) influence behavioral sensitization and display increased immediate-early gene and BDNF expressi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.04.026
更新日期：2011-09-01 00:00:00
abstract：:Histidine injected intraperitoneally into rats in doses from 400 to 800 mg/kg induced a dose-dependent bizarre behaviour. The behaviour after histidine was similar to that observed after L-DOPA and peripheral decarboxylase inhibition. The bizarre behaviour was antagonized by chloropyramine, ketotifen, clemastine and p...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90065-x
更新日期：1982-08-01 00:00:00
abstract：:Glutamate receptors play an essential role in fear-related learning and memory. The present study was designed to assess the role of the group I metabotropic glutamate receptor (mGluR) subtype 5 in the acquisition and retrieval of conditioned fear in rats. The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(01)00036-3
更新日期：2001-07-01 00:00:00
abstract：:There is strong evidence that blocking CB1 receptors may reduce alcohol intake in alcohol-dependent individuals. However, there is still limited evidence that CB1 receptor antagonists may also be beneficial in the attenuation of alcohol withdrawal syndrome, even though alcohol withdrawal appears to be milder in CB1 re...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.02.005
更新日期：2008-05-01 00:00:00
abstract：:Limited information exists on the link between purinergic class P2X7 receptors (P2X7Rs) and calcium ion channels in epilepsy; no data has been reported regarding the interaction between P2X7Rs and T-type calcium ion channels in epilepsy. Thus, this study is an evaluation of the role that T-type calcium ion channels pl...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.01.027
更新日期：2019-05-01 00:00:00
abstract：:Changes in astroglial volume were studied after incubating primary cultures from the cerebral cortex of newborn rats for 5 hr in taurine, glutamate or gamma-aminobutyric acid (GABA), alone or together with monoamine receptor agonists. Control cell volume was 2.2 microliters/mg protein. In the presence of taurine or gl...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90165-l
更新日期：1992-01-01 00:00:00
abstract：:Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.03.015
更新日期：2016-11-01 00:00:00
abstract：:In low cerveau isolé transected rats, the effects of microiontophoretic application of putative serotonin 5-HT1A and 5-HT1B agonists on the spontaneous firing rate of CA1 pyramidal cells were compared to those of 5-HT. In contrast to the large current-dependent suppression of unit activity observed with 5-HT, the 5-HT...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90079-2
更新日期：1988-07-01 00:00:00
abstract：:Muscarinic acetylcholine receptors (mAChRs) are G proteincoupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine (ACh). There are five subtypes of mAChR, M1 - M5, which are expressed throughout the central nervous system (CNS) on numerous cell types and represent promising treatment targets fo...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.11.018
更新日期：2018-07-01 00:00:00
abstract：:The cyclic octapeptide, CYN-154806, inhibited specific [(125)I]-[Tyr(11)]-SRIF binding to CHO-K1 cell membranes expressing human recombinant somatostatin (SRIF) sst(2) receptors (pIC(50) 8. 58) or rat sst(2(a)) and rat sst(2(b)) receptors (pIC(50) 8.35 and 8. 10, respectively). The affinity of CYN-154806 at other huma...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00035-6
更新日期：2000-06-08 00:00:00
abstract：:Nicotinic acetylcholine receptors (nAChRs) are considered to be viable targets to enhance cognition in patients diagnosed with schizophrenia. Activation of nAChRs with selective nicotinic receptor agonists may provide effective means to pharmacologically treat cognitive deficits observed in schizophrenia. Cognitive fl...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.01.006
更新日期：2016-06-01 00:00:00
abstract：:Methylazoxymethanol (MAM)-treated pregnant rat at gestation day (GD) 17 has been shown to be a valuable developmental animal model for schizophrenia. Yet, this model remains to be established in mice. In the present study, we examined behavioral, cytoarchitectural, and neurochemical changes in the offspring of MAM-tre...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.02.034
更新日期：2019-05-15 00:00:00
abstract：:The majority of the fibroblast growth factor receptor 1-serotonin 1 A receptor (FGFR1-5-HT1AR) heterocomplexes in the hippocampus appeared to be located mainly in the neuronal networks and a relevant target for antidepressant drugs. Through a neurochemical and electrophysiological analysis it was therefore tested in t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108070
更新日期：2020-06-15 00:00:00
abstract：:Voltage sensitivity has been demonstrated for some GPCRs. At the dopamine D(2S) receptor, this voltage sensitivity is agonist-specific; some agonists, including dopamine, exhibit decreased potency at depolarized potentials, whereas others are not significantly affected. In the present study, we examined some of the re...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.06.022
更新日期：2011-10-01 00:00:00
abstract：:Ifenprodil, which is clinically used as a cerebral vasodilator, inhibited rat brain type A (MAO-A) and type B (MAO-B) monoamine oxidase activity. It did not, however, affect rat lung semicarbazide-sensitive amine oxidase. The degree of inhibition of either form of MAO was not changed by 30 min preincubation of the enz...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90190-m
更新日期：1991-07-01 00:00:00
abstract：:Clinical evidence indicates brain serotonin (5-HT) stores and neurotransmission may be inadequate in subpopulations of individuals with autism, and this may contribute to characteristically impaired social behaviors. Findings that depletion of the 5-HT precursor tryptophan (TRP) worsens autism symptoms support this hy...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.10.024
更新日期：2015-03-01 00:00:00
abstract：:Stem cell research offers enormous potential for treating many diseases of the nervous system. At present, therapeutic strategies in stem cell research segregate into two approaches: cell transplantation or endogenous cell stimulation. Realistically, future cell therapies will most likely involve a combination of thes...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2009.10.005
更新日期：2010-05-01 00:00:00
abstract：:Epidemiological studies have reported that cigarette smoking may protect from neurodegenerative diseases such as Parkinson's disease. These protective effects are thought to be mediated by nicotine. Recent data showed that nicotine significantly decreases respiratory control ratio (RCR) and superoxide anion generation...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00041-8
更新日期：2003-04-01 00:00:00
abstract：:The postsynaptic density (PSD) at inhibitory synapses is a complex molecular assembly that serves as a platform for the interaction of neurotransmitter receptors, scaffold and adapter proteins, cytoskeletal elements and signalling molecules. The stability of the PSD depends on a multiplicity of interactions linking in...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2019.01.008
更新日期：2020-06-01 00:00:00
abstract：:Histaminergic neurons are activated by histamine H(3) receptor (H(3)R) antagonists, increasing histamine and other neurotransmitters in the brain. The prototype H(3)R antagonist thioperamide increases locomotor activity and anxiety-like behaviours; however, the mechanisms underlying these effects have not been fully e...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.02.003
更新日期：2014-06-01 00:00:00
abstract：:Electrophysiological and behavioral methods were used to evaluate and compare the effects of the competitive N-methyl-D-aspartate (NMDA) receptor blocker, NPC 12626, with the non-competitive NMDA antagonist, phencyclidine (PCP), on the activity of mesolimbic dopamine neurons. NPC 12626 (50 mg/kg, i.p.) produced a degr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90131-t
更新日期：1991-10-01 00:00:00
abstract：:Previous research shows Ouabain (OUA) to bind Na, K-ATPase, thereby triggering a number of signaling pathways, including the transcription factors NFᴋB and CREB. These transcription factors play a key role in the regulation of BDNF and WNT-β-catenin signaling cascades, which are involved in neuroprotection and memory ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.08.008
更新日期：2018-09-15 00:00:00
abstract：:Recent studies suggest a role for the arachidonic acid-derived epoxyeicosatrienoic acids (EETs) in attenuating epileptic seizures. However, their effect on neurotransmission has never been investigated in detail. Here, we studied how 11,12- and 14,15 EET affect excitability and excitatory neurotransmission in mouse hi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.05.013
更新日期：2017-09-01 00:00:00
abstract：:Centrally-administered opioid peptides produce elevations in levels of catecholamines in plasma in conscious rats. To investigate the opioid receptor involved in mediating this response, morphine (3.5-105 nmol), [D-Ala2-D-Leu5]enkephalin (DADL, 1.05-35 nmol) and U50, 488H (35-1160 nmol), relatively selective ligands f...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90047-9
更新日期：1984-11-01 00:00:00
abstract：:Dural plasma extravasation produced by electrical stimulation of the trigeminal ganglion was measured in rats and the concomitant expression of c-fos mRNA produced in the trigeminal nucleus caudalis (NtV) was measured using in situ hybridization techniques. The non-peptide NK1 receptor selective antagonist CP-99,994 (...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00153-j
更新日期：1995-03-01 00:00:00
