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 acetylcholine receptors (nAChR) containing α6β2/α4β2 subunit combinations, to provide such benefits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP) lesioned macaques with established LID. Animals were treated orally for consecutive 14-day periods with twice-daily vehicle (weeks 1-2) or TC-8831 (0.03, 0.1 or 0.3 mg/kg, weeks 3-8). L-DOPA was also administered, once-daily, (weeks 1-12, median-dose 30 mg/kg, p.o.). For the following two-weeks (weeks 9-10), TC-8831 was washed out, while once-daily L-DOPA treatment was maintained. The effects of once-daily amantadine (3 mg/kg, p.o.) were then assessed over weeks 11-12. LID, parkinsonism, duration and quality of ON-time were assessed weekly by a neurologist blinded to treatment. TC-8831 reduced the duration of 'bad' ON-time (ON-time with disabling dyskinesia) by up to 62% and decreased LID severity (median score 18 cf. 34 (vehicle), 0.1 mg/kg, 1-3 h period). TC-8831 also significantly reduced choreiform and dystonic dyskinesia (median scores 6 and 31 cf. 19 and 31 respectively (vehicle), both 0.03 mg/kg, 1-3 h). At no time did TC-8831 treatment result in a reduction in anti-parkinsonian benefit of L-DOPA. By comparison, amantadine also significantly reduced dyskinesia and decreased 'bad' ON-time (up to 61%) but at the expense of total ON-time (reduced by up to 23%). TC-8831 displayed robust anti-dyskinetic actions and improved the quality of ON-time evoked by L-DOPA without any reduction in anti-parkinsonian benefit.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Johnston TH,Huot P,Fox SH,Koprich JB,Szeliga KT,James JW,Graef JD,Letchworth SR,Jordan KG,Hill MP,Brotchie JMdoi
10.1016/j.neuropharm.2013.06.005subject
Has Abstractpub_date
2013-10-01 00:00:00pages
337-47eissn
0028-3908issn
1873-7064pii
S0028-3908(13)00265-7journal_volume
73pub_type
杂志文章abstract::Tobacco addiction is highly co-morbid with a variety of mental health conditions, including schizophrenia, mood and anxiety disorders. Nicotine, the primary psychoactive compound in tobacco-related products is known to functionally modulate brain circuits that are disturbed in these disorders. Nicotine can potently re...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2020.108411
更新日期:2021-02-15 00:00:00
abstract::The intravenous administration of L-5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), p-chloroamphetamine (PCA), LSD and methysergide to acute spinal rats, transected at C1, stimulated the flexor reflexes induced by electrical stimulation applied to the skin of the toe. The enhancement produced...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90101-8
更新日期:1987-09-01 00:00:00
abstract::Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important med...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.11.019
更新日期:2017-03-01 00:00:00
abstract::The contribution of central PGE(2) levels to the nociceptive response in rats was assessed and the effects of the selective cPLA(2)α inhibitor efipladib, and pain therapies of different classes on these responses was determined. An inflammatory pain model was optimized in rats so that PGE(2) levels in the cerebrospina...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2010.11.025
更新日期:2011-03-01 00:00:00
abstract::The effect of an acute intraperitoneal (i.p.) injection of acetaldehyde, 20 mg/kg or 100 mg/kg, on the microdialysate content of both amino acids and monoamines was studies in the nucleus accumbens (NA) by a microdialysis technique. Acetaldehyde, ACH, which was detectable at levels of 50-130 mumol/g brain tissue 10 mi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00007-5
更新日期:1997-02-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary me...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108173
更新日期:2020-09-15 00:00:00
abstract::The alpha7 and alpha4beta2 nicotinic acetylcholine receptor (nAchR) subtypes have been shown to be involved in memory. It is also known that losses of frontal cortical nAchRs are correlated to declining memory function in Alzheimer's disease, but the subtype-specific role of frontal cortical nAchRs in memory has not b...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.03.008
更新日期:2007-06-01 00:00:00
abstract::In slices of the hypothalamus of the rat, prelabelled with [3H]5-hydroxytryptamine ([3H]5-HT), dihydroergocristine (DHEC) decreased in a concentration-dependent manner (0.01-1 microM) the release of [3H]transmitter elicited by stimulation. In the presence of phentolamine (1 microM), sulpiride (1 microM), atropine (1 m...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90038-9
更新日期:1986-02-01 00:00:00
abstract::Gene-environment interactions drive experience-dependent changes in the brain that alter cognition, emotion and behaviour. Positive engagement with the environment, through novel experience and physical activity, can improve brain function, although the mechanisms mediating such experience-dependent plasticity remain ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2017.12.038
更新日期:2019-02-01 00:00:00
abstract::The binding of three, structurally distinct, 5-hydroxytryptamine3 (5-HT3) receptor radioligands was characterized in rat cerebral cortex, rabbit ileum myenteric plexus and NG-108-15 neuroblastoma cells. The density of sites labeled by the three ligands in rat cortex or in rabbit ileum was markedly different. [3H]Quipa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(93)90142-p
更新日期:1993-09-01 00:00:00
abstract::Effects of alaproclate, an inhibitor of the uptake of serotonin, on muscarinic cholinergic responses in N1E-115 neuroblastoma cells were studied using intracellular recording techniques. Application of carbachol activates an inward calcium channel, through an action on muscarinic receptors. The influx of calcium activ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90176-6
更新日期:1987-10-01 00:00:00
abstract::Antiepileptic drugs (AEDs) are widely utilized in the management of neuropathic pain. The AED valproic acid (VPA) holds out particular promise as it engages a variety of different anticonvulsant mechanisms simultaneously. However, the clinical use of VPA is limited by two rare but potentially life-threatening side eff...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.06.008
更新日期:2005-12-01 00:00:00
abstract::In this study we investigate the presence, modulation and biological function of P2 receptors and extracellular ATP in cultured cerebellar granule neurons. As we demonstrate by RT-PCR and western blotting, both P2X and P2Y receptor subtypes are expressed and furthermore regulated as a function of neuronal maturation. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00197-6
更新日期:2002-03-01 00:00:00
abstract::Receptor-mediated signal transduction is thought to play an important role in neuronal differentiation and the modification of synaptic connections during brain development. The intracellular signalling molecule phospholipase C-beta1 (PLC-beta1), which is activated via specific neurotransmitter receptors, has recently...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00056-2
更新日期:1998-04-01 00:00:00
abstract::The protopine isolated from a Chinese herb Dactylicapnos scandens Hutch was identified as an inhibitor of both serotonin transporter and noradrenaline transporter in vitro assays. 5-hydroxy-DL-tryptophan(5-HTP)-induced head twitch response (HTR) and tail suspension test were adopted to study whether protopine has anti...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.01.003
更新日期:2006-06-01 00:00:00
abstract::Phosphodiesterase 2 (PDE2) plays an important role in treatment of stress-related depression through regulation of antioxidant defense and neuroprotective mechanisms. However, the causal relationship between PDE2 and the prevalence of depression and anxiety upon exposure to oxidative stress has not been investigated. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.09.039
更新日期:2018-12-01 00:00:00
abstract::The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2017.02.013
更新日期:2017-05-01 00:00:00
abstract::Selective serotonin (5-HT) re-uptake inhibitors (SSRIs) are commonly used in the treatment of generalized anxiety disorder in Humans. However, because only few animal models display overt anxious-like behavior, detailed preclinical studies of the anxiolytic properties of antidepressants are still lacking. Here, we stu...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2011.02.009
更新日期:2011-09-01 00:00:00
abstract::Tilia species are well known around the world for their properties in traditional medicine. Antinociceptive activity of hexane, methanol and aqueous extracts from Tilia americana var. mexicana inflorescences was evaluated in the pain-induced functional impairment model in rats (PIFIR). A preliminar 300 mg/kg dosage of...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.10.010
更新日期:2009-02-01 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::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::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::Parasympathetic preganglionic cardiac vagal neurons (CVNs) which dominate the control of heart rate are located within the nucleus ambiguus (NA). Serotonin (5HT), and in particular 5HT2 receptors, play an important role in cardiovascular function in the brainstem. However, there is a lack of information on the mechani...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2008.02.016
更新日期:2008-06-01 00:00:00
abstract::Neural uptake of glutamate is executed by the structurally related members of the SLC1A family of solute transporters: GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3, EAAT4, ASCT2. These plasma membrane proteins ensure supply of glutamate, aspartate and some neutral amino acids, including glutamine and cysteine, for synthetic,...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2019.04.029
更新日期:2019-12-15 00:00:00
abstract::The ability of the enantiomers of the atypical dopamine receptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) to counteract gamma-butyrolactone-induced hyperprolactinemia was compared in male and female rats. Following gamma-butyrolactone (GBL) pretreatment serum prolactin concentrations were higher in fem...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90028-6
更新日期:1986-08-01 00:00:00
abstract::Peristaltic reflex activity in the guinea-pig isolated ileum was elicited by slow intraluminal infusion of Tyrode solution. The reflex was abolished by the ganglionic blocking drug hexamethonium. However, in more than half of the preparations, the peristaltic reflex was restored by the opioid antagonist naloxone. Hexa...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90018-9
更新日期:1987-11-01 00:00:00
abstract::Glutamic acid is the major excitatory amino acid of the central nervous system which interacts with two receptor families, the ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGluRs) are coupled to G proteins and can be divided into three subgroups based on their sequence homolog...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(96)84622-3
更新日期:1996-05-01 00:00:00
abstract::The ability of drugs of abuse to increase mesolimbic levels of dopamine is a characteristic associated with their rewarding effects. Exactly how these effects are produced by different substances is not as well characterised. Our previous work in rats has demonstrated that accumbal glycine receptors (GlyRs) are involv...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.03.010
更新日期:2014-07-01 00:00:00
abstract::In this study, a high throughput screening system was set up to identify D5 receptor agonists-027075. Then, a series of behavior tests were used to evaluate the beneficial effects of 027075 in Aβ1-42-induced mice model including morris water maze, passive avoidance, active avoidance, open field and step-down test. The...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.01.008
更新日期:2016-06-01 00:00:00
abstract::U50488H is a benzeneacetamide κ-opioid receptor (κ-OR) agonist analgesic, widely used for investigating the pharmacology of G protein-coupled κ-ORs. However, U50488H is also known to directly block various voltage-gated ion channels in a G protein-independent manner. We investigated the direct actions of U50488H on va...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.05.019
更新日期:2016-10-01 00:00:00