Abstract：
:One proposed factor contributing to the increased frequency of opioid overdose deaths is the emergence of novel synthetic opioids, including illicit fentanyl and fentanyl analogues. A treatment strategy currently under development to address the ongoing opioid crisis is immunopharmacotherapies or opioid-targeted vaccines. The present study determined the effectiveness and selectivity of a fentanyl-tetanus toxoid conjugate vaccine to alter the behavioral effects of fentanyl and a structurally dissimilar mu-opioid agonist oxycodone in male rhesus monkeys (n = 3-4). Fentanyl and oxycodone produced dose-dependent suppression of behavior in an assay of schedule-controlled responding and antinociception in an assay of thermal nociception (50 °C). Acute naltrexone (0.032 mg/kg) produced an approximate 10-fold potency shift for fentanyl to decrease operant responding. The fentanyl vaccine was administered at weeks 0, 2, 4, 9, 19, and 44 and fentanyl or oxycodone potencies in both behavioral assays were redetermined over the course of 49 weeks. The vaccine significantly and selectively shifted fentanyl potency at least 10-fold in both assays at several time points over the entire experimental period. Mid-point titer levels correlated with fentanyl antinociceptive potency shifts. Antibody affinity for fentanyl as measured by a competitive binding assay improved over time to approximately 3-4 nM. The fentanyl vaccine also increased fentanyl plasma levels approximately 6-fold consistent with the hypothesis that the vaccine sequesters fentanyl in the blood. Overall, these results support the continued development and evaluation of this fentanyl vaccine in humans to address the ongoing opioid crisis.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Tenney RD,Blake S,Bremer PT,Zhou B,Hwang CS,Poklis JL,Janda KD,Banks MLdoi
10.1016/j.neuropharm.2019.107730subject
Has Abstractpub_date
2019-11-01 00:00:00pages
107730eissn
0028-3908issn
1873-7064pii
S0028-3908(19)30289-8journal_volume
158pub_type
杂志文章abstract：:Attentional impairments are found in a range of neurodegenerative and neuropsychiatric disorders. However, the development of procognitive enhancers to alleviate these impairments has been hindered by a lack of comprehensive hypotheses regarding the circuitry mediating the targeted attentional functions. Here we discu...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2012.06.060
更新日期：2013-01-01 00:00:00
abstract：:Painful nerve injury disrupts Ca2+ signaling in primary sensory neurons by elevating plasma membrane Ca2+-ATPase (PMCA) function and depressing sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) function, which decreases endoplasmic reticulum (ER) Ca2+ stores and stimulates store-operated Ca2+ entry (SOCE). The extracell...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.02.019
更新日期：2017-05-01 00:00:00
abstract：:The effects of thyrotropin-releasing hormone (TRH) and an analog of this hormone, MK-771, were determined on body shaking behavior and on biochemical estimates of the activity of dopamine (DA) neurons in the rat. Both compounds elicited dose-related episodes of "wet-dog shakes". A dose of TRH (20 mg/kg, i.p.) which ca...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90105-9
更新日期：1984-07-01 00:00:00
abstract：:The N-methyl-d-aspartate (NMDA) receptor is a key target of ethanol action in the central nervous system. Alcohol inhibition of NMDA receptor function involves small clusters of residues in the third and fourth membrane-associated (M) domains. Previous results from this laboratory have shown that two adjacent position...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.11.013
更新日期：2017-03-01 00:00:00
abstract：:Intraventricular administration of substance P (SP), of the heptapeptide SP5-11 and of DiMe-C7, a stable analogue of SP5-11 induced locomotor activation in rats and in mice. The activating effect of substance P was longer-lasting in mice than in rats, whereas the effect of the two heptapeptides appears to be more mark...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90234-x
更新日期：1984-10-01 00:00:00
abstract：:Biochemical, behavioral and electrophysiological evidence suggests interactions between pathways containing neuronal nicotinic acetylcholine receptors (NAChRs) and excitatory amino acid receptors. Recently, protective effects of nicotine against N-methyl-D-aspartate (NMDA)-induced toxicity in primary cortical cultures...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00162-1
更新日期：1997-01-01 00:00:00
abstract：:Glutamatergic neurotransmission in the CNS plays a predominant role in learning and memory. While NMDA receptors have been extensively studied, less is known about the involvement of group I metabotropic glutamate receptors in this area. The purpose of the present study was to evaluate the contribution of mGluR1 and m...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.07.008
更新日期：2006-12-01 00:00:00
abstract：:The mechanisms underlying lateralization and progression of motor symptoms from unilateral to bilateral in Parkinson's disease (PD) remain to be elucidated. In addition, the molecular mechanisms involved in levodopa-induced dyskinesias (LIDs) depending on lateralization and disease progression from unilaterally to bil...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.06.004
更新日期：2015-10-01 00:00:00
abstract：:Recent observations from synaptosome preparations have questioned the tetrodotoxin (TTX) insensitivity of nicotine-evoked release in the striatum, a characteristic previously considered diagnostic of presynaptically located nicotinic acetylcholine receptors (nAChRs). Therefore, we have undertaken a comparison of nicot...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(96)00117-7
更新日期：1996-01-01 00:00:00
abstract：:The identification and characterization of amyloid-beta (Abeta) and tau as the main pathological substrates of Alzheimer's disease (AD) have driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that go...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2010.04.006
更新日期：2010-09-01 00:00:00
abstract：:The potential role of N-linked glycosylation of the human type 1alpha metabotropic glutamate (mGlu1alpha) receptor was studied in a recombinant, inducible expression system, where receptor expression was induced in the absence and presence of tunicamycin. In the absence of tunicamycin the mGlu1alpha receptor appeared ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00099-4
更新日期：1999-10-01 00:00:00
abstract：:Thiamethoxam (TMX) is a second-generation neonicotinoid which is known to induce toxic effects on insects and mammalians. Recently, it has been proposed that TMX is a poor agonist of insect nicotinic acetylcholine receptors (nAChRs) on isolated cell bodies. Here, we have studied its effect on synaptic transmission. Ou...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.12.008
更新日期：2011-03-01 00:00:00
abstract：:We have examined the effects of a variety of classical and atypical neuroleptic drugs on mitochondrial NADH ubiquinone oxido-reductase (complex I) activity. Sagittal slices of mouse brain incubated in vitro with haloperidol (10 nM) showed time- and concentration-dependent inhibition of complex I. Similar concentration...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00215-9
更新日期：1999-04-01 00:00:00
abstract：:We investigated the effect of 5-HT6 receptor subtype activation on glutamatergic transmission by means of whole-cell patch-clamp electrophysiological recordings from medium spiny neurons of the striatum and layer V pyramidal neurons of the prefrontal cortex. To this aim, we took advantage of a novel ligand, ST1936, sh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.05.004
更新日期：2011-09-01 00:00:00
abstract：:G protein regulated inward rectifying potassium channels (GIRKs) are activated by G protein coupled receptors (GPCRs) via the G protein betagamma subunits. However, little is known about the effects of different GPCRs on the deactivation kinetics of transmitter-mediated GIRK currents. In the present study we investiga...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00080-0
更新日期：2000-09-01 00:00:00
abstract：:Effective medical treatment for impulsive aggression and several impulse control disorders is needed. Disinhibited, impulsive behavior of e.g. murderers, arsonists, suicidal patients, and patients suffering from antisocial personality or substance abuse disorders has been associated with signs of a deficiency in brain...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00076-3
更新日期：1999-12-01 00:00:00
abstract：:The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did n...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(84)80002-7
更新日期：1984-02-01 00:00:00
abstract：:Though amyloid precursor protein (APP) can potentially be cleaved to generate the pathological amyloid β peptide (Aβ), APP itself plays an important role in regulating neuronal activity. APP deficiency causes functional impairment in cholinergic synaptic transmission and cognitive performance. However, the mechanisms ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.08.021
更新日期：2016-11-01 00:00:00
abstract：:Schizophrenic patients have been shown to exhibit abnormal cortical gamma band oscillation (GBO), which is thought to be related to the symptoms of schizophrenia, including cognitive impairment. Recently, non-competitive NMDA receptor (NMDAr) antagonists such as MK-801 and ketamine have been reported to increase the b...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.05.037
更新日期：2014-10-01 00:00:00
abstract：:In the cerebellum of juvenile mice or rats, endocannabinoids are shown to mediate depolarization-induced suppression of excitation (DSE) and retrograde suppression induced by activation of type 1 metabotropic glutamate receptor (mGluR1) at parallel fiber (PF) to Purkinje cell (PC) synapses. However, recent studies sho...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.04.015
更新日期：2009-08-01 00:00:00
abstract：:In the solitary tract nucleus, neuronal responsiveness to synaptic input from peripheral afferent fibres has been found to decrease as the frequency of that input is increased. The present study investigated the possibility that glycine and gamma-aminobutyric acid (GABA) are (1) involved in this phenomenon of "frequen...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90149-6
更新日期：1991-03-01 00:00:00
abstract：:The properties of central ATP-mediated synaptic currents were studied using whole-cell patch-clamp recording in rat medial habenula slices. Release was shown to be calcium dependent with a Hill coefficient of approximately 2. The voltage dependence of synaptic current amplitudes was approximately linear. Some reductio...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00127-5
更新日期：1997-09-01 00:00:00
abstract：:Hypotheses are scaffoldings erected in front of a building and then dismantled when the building is finished. They are indispensable for the workman; but you mustn't mistake the scaffolding for the building. Johann Wolfgang von Goethe. The neurogenesis hypothesis of affective disorders - in its simplest form - postula...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2011.09.003
更新日期：2012-01-01 00:00:00
abstract：:Neurotrophins jointly exert various functions in the nervous system, including neuronal differentiation, survival, and regulation of synaptic plasticity. However, the functional interactions of neurotrophins or mechanisms through which neurotrophins regulate each other are still not clear. In the present study, brain-...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00043-6
更新日期：2002-06-01 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：:Slow excitatory postsynaptic currents (EPSCs) mediated by metabotropic glutamate receptors (mGlu receptors) have been reported in several neuronal subtypes, but their presence in hippocampal pyramidal neurons remains elusive. Here we find that in CA1 pyramidal neurons a slow EPSC is induced by repetitive stimulation w...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.08.028
更新日期：2017-03-15 00:00:00
abstract：:It has been hypothesized that Acetyl-L-Carnitine (ALC) contributes to mitochondrial ATP production through maintenance of key mitochondrial proteins and protects mitochondria against oxidative stress. We have investigated the role of ALC on the expression of two forms of synaptic plasticity in the striatum: (i) the ph...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.05.015
更新日期：2008-08-01 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：:The effect of nifedipine, a calcium channel antagonist, on changes in the density of glucocorticoid (GR) and/or mineralocorticoid receptors (MR), induced by long-term treatment with antidepressant drugs (imipramine and amitriptyline) or electroconvulsive shock (ECS) was investigated in the rat hippocampus. Long-term t...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90036-3
更新日期：1993-12-01 00:00:00
abstract：:Our understanding of the role GABA(C) receptors play in the central nervous system is limited due to a lack of specific ligands. Here we describe the pharmacological effects of (+/-)-cis-3- and (+/-)-trans-3-(aminocyclopentyl)methylphosphinic acids ((+/-)-cis- and (+/-)-trans-3-ACPMPA) as novel ligands for the GABA(C)...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.09.014
更新日期：2007-03-01 00:00:00
