keyword
MENU ▼
Read by QxMD icon Read
search

Ampakine

keyword
https://www.readbyqxmd.com/read/29906466/tarps-differentially-affect-the-pharmacology-of-ampakines
#1
Daniel P Radin, Yong-Xin Li, Gary Rogers, Richard Purcell, Arnold Lippa
Transmembrane AMPA receptor regulatory proteins (TARPs) govern AMPA receptor cell surface expression and distinct physiological properties including agonist affinity, desensitization and deactivation kinetics. The prototypical TARP, STG or γ2 and TARPs γ3, γ4, γ7 and γ8 are all expressed to varying degrees in the mammalian brain and differentially regulate AMPAR gating parameters. Positive allosteric AMPA receptor modulators or ampakines alter receptor rates of agonist binding/unbinding, channel opening and can offset receptor desensitization and deactivation...
June 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29886374/effects-of-chronic-systemic-low-impact-ampakine-treatment-on-neurotrophin-expression-in-rat-brain
#2
Daniel P Radin, Steven Johnson, Richard Purcell, Arnold S Lippa
Neurotrophin dysregulation has been implicated in a large number of neurodegenerative and neuropsychiatric diseases. Unfortunately, neurotrophins cannot cross the blood brain barrier thus, novel means of up regulating their expression are greatly needed. It has been demonstrated previously that neurotrophins are up regulated in response to increases in brain activity. Therefore, molecules that act as cognitive enhancers may provide a clinical means of up regulating neurotrophin expression. Ampakines are a class of molecules that act as positive allosteric modulators of AMPA-type glutamate receptors...
June 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29848697/ampakines-attenuate-staurosporine-induced-cell-death-in-primary-cortical-neurons-implications-in-the-chemo-brain-phenomenon
#3
Daniel P Radin, Gary A Rogers, Kimberley E Hewitt, Richard Purcell, Arnold Lippa
BACKGROUND/AIM: Mounting evidence suggests that trophic cell signaling can be mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation. It has been demonstrated that exogenous application of brain-derived neurotrophic factor (BDNF) is highly neuroprotective in vitro against neurotoxic insults such as standard chemotherapies. MATERIALS AND METHODS: Because positive allosteric modulation of AMPARs with ampakines can increase both BDNF mRNA and protein in vitro and in vivo, we examined whether application of the ampakines CX614 and CX729 promoted neuroprotection against staurosporine-induced cell death in rat primary cortical neurons using propidium iodide to stain for dead cells...
June 2018: Anticancer Research
https://www.readbyqxmd.com/read/29553984/averting-opioid-induced-respiratory-depression-without-affecting-analgesia
#4
Albert Dahan, Rutger van der Schrier, Terry Smith, Leon Aarts, Monique van Velzen, Marieke Niesters
The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication that may occur when opioids are overdosed or consumed in combination with other depressants such as sleep medication or alcohol. Fatalities occur in acute and chronic pain patients on opioid therapy and individuals that abuse prescription or illicit opioids for their hedonistic pleasure. One important strategy to mitigate opioid-induced respiratory depression is cotreatment with nonopioid respiratory stimulants...
May 2018: Anesthesiology
https://www.readbyqxmd.com/read/29370673/arc-arg3-1-protein-expression-in-dorsal-hippocampal-ca1-a-candidate-event-as-a-biomarker-for-the-effects-of-exercise-on-chronic-stress-evoked-behavioral-abnormalities
#5
Yea-Hyun Leem, Hyukki Chang
PURPOSE: Chronic stress is a risk factor for behavioral deficits, including impaired memory processing and depression. Exercise is well known to have beneficial impacts on brain health. METHODS: Mice were forced to treadmill running (4-week) during chronic restraint stress (6h/21d), and then behavioral tests were conducted by Novel object recognition, forced swimming test: FST, sociality test: SI. Dissected brain was stained with anti-calbindin-d28k and anti-Arc antibodies...
December 31, 2017: Journal of Exercise Nutrition & Biochemistry
https://www.readbyqxmd.com/read/29330065/stargazin-differentially-modulates-ampakine-gating-kinetics-and-pharmacology
#6
Daniel P Radin, Yong-Xin Li, Gary Rogers, Richard Purcell, Arnold Lippa
It was previously reported that Stargazin (STG) enhances the surface expression of AMPA receptors, controls receptor gating and slows channel desensitization as an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor positive allosteric modulators that modify rates of transmitter binding, channel activity and desensitization parameters. As such, they have shown efficacy in animal models of neurodegenerative diseases, where excitatory synaptic transmission is compromised. Given the functional similarities between STG and ampakines, the current study sought to probe interactions between STG and ampakine gating properties...
February 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29277782/oncolytic-properties-of-ampakines-in-vitro
#7
Daniel P Radin, Richard Purcell, Arnold S Lippa
BACKGROUND/AIM: The 5-year survival rate of glioblastoma (GBM) is ~10%, demonstrating that a new therapeutic modality for this cancer is desperately needed. Complicating the search for such a modality is that most large molecules cannot pass through the blood brain barrier, so molecules demonstrating efficacy in vitro may not be useful in vivo because they never reach the brain. Recently, the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) was identified as an effective agent in targeting GBM in vitro and in vivo by agonizing AMPA-glutamate receptors (AMPARs), eliciting massive calcium influx and mitochondrial calcium overload and apoptosis...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29108612/sleep-disordered-breathing-caused-by-chronic-opioid-use-diverse-manifestations-and-their-management
#8
REVIEW
Susmita Chowdhuri, Shahrokh Javaheri
Opioid-induced sleep disordered breathing presents a therapeutic predicament with the increasing incidence of prescription opioid use for noncancer chronic pain in the United States. Central sleep apnea with a Biot or cluster breathing pattern is characteristic of polysomnography studies; however, long-term clinical outcomes and the impact of therapy remain unknown. Novel ampakine-based therapies are being investigated. Randomized controlled trials with therapies that target the underlying pathophysiologic mechanisms of opioid-induced sleep disordered breathing are required...
December 2017: Sleep Medicine Clinics
https://www.readbyqxmd.com/read/29040524/potentiation-of-excitatory-synaptic-transmission-ameliorates-aggression-in-mice-with-stxbp1-haploinsufficiency
#9
Hiroyuki Miyamoto, Atsushi Shimohata, Manabu Abe, Teruo Abe, Emi Mazaki, Kenji Amano, Toshimitsu Suzuki, Tetsuya Tatsukawa, Shigeyoshi Itohara, Kenji Sakimura, Kazuhiro Yamakawa
Genetic studies point to a major role of de novo mutations in neurodevelopmental disorders of intellectual disability, autism spectrum disorders, and epileptic encephalopathy. The STXBP1 gene encodes the syntaxin-binding protein 1 (Munc18-1) that critically controls synaptic vesicle exocytosis and synaptic transmission. This gene harbors a high frequency of de novo mutations, which may play roles in these neurodevelopmental disorders. However, the system and behavioral-level pathophysiological changes caused by these genetic defects remain poorly understood...
December 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28968657/pharmacological-modulation-of-ampar-rescues-intellectual-disability-like-phenotype-in-tm4sf2-y-mice
#10
Luca Murru, Elena Vezzoli, Anna Longatti, Luisa Ponzoni, Andrea Falqui, Alessandra Folci, Edoardo Moretto, Veronica Bianchi, Daniela Braida, Mariaelvina Sala, Patrizia D'Adamo, Silvia Bassani, Maura Francolini, Maria Passafaro
Intellectual disability affects 2-3% of the world's population and typically begins during childhood, causing impairments in social skills and cognitive abilities. Mutations in the TM4SF2 gene, which encodes the TSPAN7 protein, cause a severe form of intellectual disability, and currently, no therapy is able to ameliorate this cognitive impairment. We previously reported that, in cultured neurons, shRNA-mediated down-regulation of TSPAN7 affects AMPAR trafficking by enhancing PICK1-GluA2 interaction, thereby increasing the intracellular retention of AMPAR...
August 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28950762/positive-modulation-of-ampa-receptors-promotes-survival-and-proliferation-of-neural-stem-progenitor-cells-from-the-adult-rat-spinal-cord
#11
Laureen D Hachem, Andrea J Mothe, Charles H Tator
Transplantation of neural stem/progenitor cells (NSPCs) following spinal cord injury (SCI) is a promising strategy to enhance regeneration but is limited by poor survival of grafted cells. Determining methods to enhance survival of NSPCs is therefore essential. Positive modulation of AMPA receptors has been shown to enhance neurogenesis in various models of brain injury. Here we examined the effect of selective AMPA receptor modulation in adult rat spinal cord-derived NSPCs using a class of allosteric AMPA receptor modulators known as ampakines...
December 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28734765/ampakines-and-morphine-provide-complementary-analgesia
#12
Yongjun Sun, Kevin Liu, Erik Martinez, Jahrane Dale, Dong Huang, Jing Wang
Glutamate signaling in the central nervous system is known to play a key role in pain regulation. AMPAkines can enhance glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. previous studies have shown that AMPAkines are effective analgesic agents, and their site of action is likely in the brain. It is not known, however, if AMPAkines can provide complementary analgesia in combination with opioids, the most commonly used analgesics. Here, we show that the co-administration of an AMPAkine with morphine can provide additional analgesia, both in naïve rats and in rats that experience postoperative pain...
September 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28502631/a-brain-targeted-ampakine-compound-protects-against-opioid-induced-respiratory-depression
#13
Wei Dai, Dian Xiao, Xiang Gao, Xin-Bo Zhou, Tong-Yu Fang, Zheng Yong, Rui-Bin Su
The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression...
August 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27721179/acute-ampakine-treatment-ameliorates-age-related-deficits-in-long-term-potentiation
#14
Daniel P Radin, Sheng Zhong, Richard Purcell, Arnold Lippa
Memory loss observed as a consequence of aging is paralleled by a down-regulation of AMPA-type glutamate receptors (AMPARs) that mediate fast excitatory synaptic transmission. Activation of these receptors enhances long-term potentiation (LTP), a neuronal process demonstrated to be crucial for memory storage and thought to be a cellular substrate of learning and memory. In the present studies, we determined that LTP was reduced in aged rats when compared to young rats and that acute treatment with CX1846, a novel AMPAR positive allosteric modulator, fifteen minutes prior to tetanic stimulation completely reversed the significant deficit in LTP observed in aged rats...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27627816/ampakines-target-the-nucleus-accumbens-to-relieve-postoperative-pain
#15
Chen Su, Hau Yeuh Lin, Runtao Yang, Duo Xu, Michelle Lee, Natalie Pawlak, Monica Norcini, Alexandra Sideris, Esperanza Recio-Pinto, Dong Huang, Jing Wang
BACKGROUND: AMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive. METHODS: The authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain...
November 2016: Anesthesiology
https://www.readbyqxmd.com/read/27531058/ampakine-cx1942-attenuates-opioid-induced-respiratory-depression-and-corrects-the-hypoxaemic-effects-of-etorphine-in-immobilized-goats-capra-hircus
#16
COMPARATIVE STUDY
Anna J Haw, Leith Cr Meyer, John J Greer, Andrea Fuller
OBJECTIVES: To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. STUDY DESIGN: A prospective, crossover experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. METHODS: Following immobilization with 0.1 mg kg(-1) etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials...
September 2016: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/27334260/post-anesthesia-ampa-receptor-potentiation-prevents-anesthesia-induced-learning-and-synaptic-deficits
#17
Lianyan Huang, Joseph Cichon, Ipe Ninan, Guang Yang
Accumulating evidence has shown that repeated exposure to general anesthesia during critical stages of brain development results in long-lasting behavioral deficits later in life. To date, there has been no effective treatment to mitigate the neurotoxic effects of anesthesia on brain development. By performing calcium imaging in the mouse motor cortex, we show that ketamine anesthesia causes a marked and prolonged reduction in neuronal activity during the period of post-anesthesia recovery. Administration of the AMPAkine drug CX546 [1-(1,4-benzodioxan-6-ylcarbonyl)piperidine] to potentiate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activity during emergence from anesthesia in mice enhances neuronal activity and prevents long-term motor learning deficits induced by repeated neonatal anesthesia...
June 22, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27306673/ampakine-cx717-potentiates-intermittent-hypoxia-induced-hypoglossal-long-term-facilitation
#18
S M Turner, M K ElMallah, A K Hoyt, J J Greer, D D Fuller
Glutamatergic currents play a fundamental role in regulating respiratory motor output and are partially mediated by α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors throughout the premotor and motor respiratory circuitry. Ampakines are pharmacological compounds that enhance glutamatergic transmission by altering AMPA receptor channel kinetics. Here, we examined if ampakines alter the expression of respiratory long-term facilitation (LTF), a form of neuroplasticity manifested as a persistent increase in inspiratory activity following brief periods of reduced O2 [intermittent hypoxia (IH)]...
September 1, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27147648/optogenetic-stimulation-of-prefrontal-glutamatergic-neurons-enhances-recognition-memory
#19
Abigail Benn, Gareth R I Barker, Sarah A Stuart, Eva V L Roloff, Anja G Teschemacher, E Clea Warburton, Emma S J Robinson
UNLABELLED: Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically...
May 4, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27089316/design-synthesis-and-biological-evaluation-of-brain-targeted-thiamine-disulfide-prodrugs-of-ampakine-compound-lcx001
#20
Dian Xiao, Fan-Hua Meng, Wei Dai, Zheng Yong, Jin-Qiu Liu, Xin-Bo Zhou, Song Li
Ampakine compounds have been shown to reverse opiate-induced respiratory depression by activation of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. However, their pharmacological exploitations are hindered by low blood-brain barrier (BBB) permeability and limited brain distribution. Here, we explored whether thiamine disulfide prodrugs with the ability of "lock-in" can be used to solve these problems. A series of thiamine disulfide prodrugs 7a-7f of ampakine compound LCX001 was synthesized and evaluated...
April 14, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
keyword
keyword
62272
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"