Abstract：
:Efficient transcytosis across the blood-brain-barrier (BBB) is an important strategy for accessing drug targets within the central nervous system (CNS). Despite extensive research the number of studies reporting successful delivery of macromolecules or macromolecular complexes to the CNS has remained very low. In order to expand current research it is important to know which receptors are selective and abundant on the BBB so that novel CNS-targeting antibodies or other ligands could be developed, targeting those receptors for transcytosis. To do that, we have set up a proteomics- and transcriptomics-based workflow within the COMPACT project (Collaboration on the Optimization of Macromolecular Pharmaceutical Access to Cellular Targets) of the Innovative Medicines Initiative (IMI) of the EU. Here we summarise our overall strategy in endothelial transcytosis research, describe in detail the related challenges, and discuss future perspectives of these studies. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders".
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Mäger I,Meyer AH,Li J,Lenter M,Hildebrandt T,Leparc G,Wood MJAdoi
10.1016/j.neuropharm.2016.08.025subject
Has Abstractpub_date
2017-07-01 00:00:00pages
4-7eissn
0028-3908issn
1873-7064pii
S0028-3908(16)30361-6journal_volume
120pub_type
杂志文章,评审abstract：:Opioids are thought to increase the excitability of hippocampal pyramidal cells by decreasing release of neurotransmitter from inhibitory interneurons. This study compared the actions of the opioid agonist normorphine, and the GABA receptor antagonist bicuculline, on the responses of CA1 pyramidal cells to afferent st...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90152-4
更新日期：1989-07-01 00:00:00
abstract：:The effects of injection of the thyrotrophin-releasing hormone (TRH) analogue, orotyl-histidyl-proline amide (CG3509) into the accumbens and striatum, was studied on dopamine metabolism by means of in vivo voltammetry. Forty minutes after infusion of CG3509 (1-5 micrograms) into the n. accumbens there was a significan...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90141-2
更新日期：1984-06-01 00:00:00
abstract：:The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but n...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90185-6
更新日期：1985-11-01 00:00:00
abstract：:Endogenous interferon beta (IFNβ) is an important cytokine involved in several chronic inflammatory diseases, such as Multiple Sclerosis (MS). In spite of the numerous therapeutic approaches available for MS patients, the administration of recombinant IFNβ continues being one of the first line treatment to these patie...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.07.026
更新日期：2016-11-01 00:00:00
abstract：:The proconvulsant and anticonvulsant effects of acute and chronic exposure to cocaine were investigated in adult, male, CF-1 mice. The proconvulsant effects of cocaine in mice only manifested themselves after daily exposure to motor-stimulant doses. Although daily treatment decreased electroshock convulsion threshold,...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90155-x
更新日期：1989-07-01 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：:4-Aminopyridine (4-AP) stimulated the release of [3H]dopamine from striatal synaptosomes in the rat. At a concentration of 200 microM, 4-aminopyridine increased the spontaneous efflux of dopamine by 170%. The effect of 4-aminopyridine was calcium-dependent, being abolished when calcium was omitted from the incubation ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90083-3
更新日期：1986-07-01 00:00:00
abstract：:Sodium (Na) channel blockers are known to possess antihyperalgesic properties. We have designed and synthesized a novel Na channel antagonist, alpha-hydroxyphenylamide, and determined its ability to inhibit both TTX-sensitive (TTX-s) and TTX-resistant (TTX-r) Na currents from small dorsal root ganglion (DRG) neurons. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.12.008
更新日期：2006-06-01 00:00:00
abstract：:Using knockout (KO) mice lacking the histamine (HA)-synthesizing enzyme (histidine decarboxylase, HDC), we have previously shown the importance of histaminergic neurons in maintaining wakefulness (W) under behavioral challenges. Since the central actions of HA are mediated by several receptor subtypes, it remains to b...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.12.014
更新日期：2016-07-01 00:00:00
abstract：:It is well established that some members of the Deg/ENaC super family of amiloride sensitive ion channels can participate directly in the transduction of mechanical stimuli by sensory neurons in invertebrates. A large body of work has also implicated the acid sensing ion channels family (ASIC1-4) as participants in re...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2014.12.007
更新日期：2015-07-01 00:00:00
abstract：:The effects of pretreatment of rats with an intrahypothalamic injection of 6-hydroxydopamine on the thermal responses induced by intrahypothalamic injection of noradrenaline, prostaglandin E2, thyrotropin-releasing hormone or beta-endorphin were assessed. Administration of either noradrenaline (2-10 micrograms), prost...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(85)90188-1
更新日期：1985-11-01 00:00:00
abstract：:The dopaminergic receptors of planaria have been studied with pharmacological and biochemical criteria. Dopamine D1 selective agonists (CY 208243 (10 micrograms/ml) and SKF 38393 (10 micrograms/ml] induced in planaria typical screw-like hyperkinesias, that were inhibited by a D1 antagonist (SCH 23390 (10 micrograms/ml...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90013-0
更新日期：1989-12-01 00:00:00
abstract：:Mice were found to exhibit a marked suppression of motor activity when placed into the same experimental chamber in which they had previously received electrical shocks. This suppression was found to be a stable response when mice, 6-8 weeks of age, received shocks of frequencies of 1/10 or 1/30 Hz, and their motility...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90134-4
更新日期：1982-12-01 00:00:00
abstract：:4-Alkylated analogues of homoibotenic acid (HIBO) have previously shown high potency and selectivity at ionotropic and metabotropic glutamic acid receptor (iGluR and mGluR) subtypes. Compounds with different selectivity profiles are valuable pharmacological tools for neuropharmacological studies, and the series of 4-a...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.05.007
更新日期：2005-01-01 00:00:00
abstract：:Owing to a broad spectrum of functions performed by neuropeptides, this class of signaling molecules attracts an increasing interest. One of the key steps in the regulation of biological activity of neuropeptides is proteolytic conversion or degradation by proteinases that change or terminate biological activity of na...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108137
更新日期：2020-09-15 00:00:00
abstract：:We investigated the effects of salvinorin A on the basal and the 12 mM K(+)-evoked release of preloaded [(3)H]noradenaline ([(3)H]NA) and [(3)H]serotonin ([(3)H]5-HT) from mouse hippocampal nerve terminals (synaptosomes), as well as on the basal and 12mM K(+)-evoked release of preloaded [(3)H]dopamine ([(3)H]DA) from ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.07.023
更新日期：2009-10-01 00:00:00
abstract：:Trace amines are biological compounds that are still awaiting identification of their role in neuronal function. Using intracellular electrophysiological recordings, we investigated the depressant action of two trace amines (beta-phenylethylamine and tyramine) on the firing activity of dopaminergic neurons of the subs...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.11.031
更新日期：2004-05-01 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：:Traumatic injuries to peripheral nerves are frequent, however, specific pharmacological treatments are currently lacking. Curcumin has antioxidant, anti-inflammatory and neuroprotective properties but high oral doses are required for therapeutic use, particularly due to its low bioavailability. The aim of the present ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.07.001
更新日期：2018-09-01 00:00:00
abstract：:In this study, the P2 receptor-mediated modulation of [3H]glutamate and [3H]noradrenaline release were examined in rat spinal cord slices. Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and 2-methylthioadenosine 5'-diphosphate (2-MeSADP) decreased the electrical stimulation-evoked [3H]glutamate efflu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.10.013
更新日期：2008-02-01 00:00:00
abstract：:Dopamine denervation in Parkinson's disease and repeated Levodopa (L-DOPA) administration that induces dyskinesias are associated with an enhancement of basal ganglia neuropeptide transmission. Various adjunct non-dopaminergic treatments to Levodopa were shown to reduce and/or prevent dyskinesias. The aim of this stud...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.06.030
更新日期：2010-01-01 00:00:00
abstract：:A neuronal nicotinic acetylcholine receptor (nAChR) subunit, Dalpha4, has been identified and cloned from the fruit fly Drosophila melanogaster, together with several alternatively spliced transcripts. Intron-exon boundaries within the gene encoding Dalpha4 (nAcRalpha-80B) have been identified by comparison of cDNA an...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00111-8
更新日期：2000-10-01 00:00:00
abstract：:The group II metabotropic glutamate receptor (mGluR) antagonists LY341495 and LY366457 were profiled for their effects on locomotor activity in mice. Both compounds significantly increased locomotor activity. Observational studies showed that rearing was also selectively increased. LY366457-induced hyperactivity was s...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00232-6
更新日期：2003-10-01 00:00:00
abstract：:The cognitive impairments and negative symptoms experienced by schizophrenia patients still await effective treatment. Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) have gain considerable attention in this regard. It has been recently proposed that positive allosteric modulators (PAMs) of α7 nAChRs may represen...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.10.002
更新日期：2017-02-01 00:00:00
abstract：:A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer's disease. Compounds that act as positive allosteric modulators at GABA(A) α5 receptors might be useful in targeting this condition because GABA(A) α5 rece...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2012.06.023
更新日期：2013-01-01 00:00:00
abstract：:We investigated the anti-inflammatory effects of acetylcholinesterase inhibitors (AChEI) at the cellular and molecular levels. AChEI suppressed lymphocyte proliferation and pro-inflammatory cytokine production, as well as extracellular esterase activity. Anti-inflammatory activity was mediated by the alpha7 nicotinic ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.10.013
更新日期：2006-04-01 00:00:00
abstract：:Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperito...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.10.013
更新日期：2016-02-01 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：:Midazolam, which induces anaesthesia in humans at intravenous doses of 0.3 mg/kg, did not anaesthetize cats at doses of 20 mg/kg. Nevertheless, intravenous doses as small as 0.3 mg/kg enhanced spinal primary afferent depolarization and presynaptic inhibition of spinal monosynaptic reflexes, and both intravenous and mi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90223-x
更新日期：1983-12-01 00:00:00
abstract：:Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the nervous system and are implicated in many normal and pathological processes. The structural determinants of allostery in nAChRs are not well understood. One class of nAChR allosteric modulators, including the small molecule morantel (Mor...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.11.027
更新日期：2015-04-01 00:00:00
