journal
MENU ▼
Read by QxMD icon Read
search

Journal of Pharmacology and Experimental Therapeutics

journal
https://www.readbyqxmd.com/read/29222131/low-dose-anthracycline-and-risk-of-heart-failure-in-a-pharmacokinetic-model-of-human-myocardium-exposure-analog-specificity-and-role-of-secondary-alcohol-metabolites
#1
Emanuela Salvatorelli, Pierantonio Menna, Massimo Chello, Elvio Covino, Giorgio Minotti
Cumulative doses of doxorubicin and other antitumor anthracyclines may cause heart failure (HF). Cardiotoxicity is determined by cardiac exposure to anthracyclines and to more toxic secondary alcohol metabolites that are formed inside cardiomyocytes or diffuse from the bloodstream. Concerns exist that HF might be caused by cumulative anthracycline doses that were thought to be safe. Patients with gain-of-function polymorphism of carbonyl reductase 3 (CBR3), which converts anthracyclines to secondary alcohol metabolites, would be at a higher risk of HF...
December 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29217540/cancer-stem-cell-suppressing-activity-of-chrysotoxine-a-bibenzyl-from-dendrobium-pulchellum
#2
Narumol Bhummaphan, Varisa Pongrakhananon, Boonchoo Sritularak, Pithi Chanvorachote
Cancer stem cells (CSCs) have been recognized as rare populations driving cancer progression, metastasis, and drug resistance in leading cancers. Attempts have been paid toward identifying compound that specifically targets these CSCs. Therefore, the investigations of the novel therapeutic strategies for CSCs targeting is required. The cytotoxic effects of Chrysotoxine on human NSCLC-derived H460 and H23 cells were tested by MTT assay. The Effect of Chrysotoxine suppresses CSC-like phenotypes was determined in CSC-rich populations and primary CSCs in 3D culture and Extreme limiting dilution assay...
December 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29217539/inhibition-of-cocaine-and-3-4-methylenedioxypyrovalerone-mdpv-self-administration-by-lorcaserin-is-mediated-by-5-ht2c-receptors-in-rats
#3
Brenda M Gannon, Agnieszka Sulima, Kenner C Rice, Gregory T Collins
Lorcaserin is a serotonin (5-HT)2C receptor-preferring agonist approved by the US Food and Drug Administration to treat obesity. Lorcaserin has been shown to decrease cocaine self-administration in rats and monkeys. Although this effect is partially inhibited by a 5-HT2C receptor antagonist (SB 242084), lorcaserin also has effects at 5-HT2A and 5-HT1A receptors and the relative contribution of these receptors to its anti-cocaine effects has not been investigated. The goals of this study were to determine: (1) the potency and effectiveness of lorcaserin to decrease self-administration of cocaine and 3,4-methylenedioxypyrovalerone (MDPV), a common "bath salts" constituent; and (2) the receptor(s) mediating the effects of lorcaserin on cocaine and MDPV self-administration...
December 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29212832/adenosine-a-2a-receptor-agonist-2-p-2-carboxyethyl-phenethylamino-5-n-ethylcarboxamidoadenosine-hydrochloride-hydrate-cgs21680-inhibits-inflammation-and-increases-fibroblast-growth-factor-2-fgf-2-tissue-expression-in-carrageenan-induced-rat-paw-edema
#4
Armando Ialenti, Elisabetta Caiazzo, Silvana Morello, Rosa Carnuccio, Carla Cicala
Adenosine is the final product of ATP metabolism, mainly derived from the action of 5'-nucleotidase cleavage of AMP. Cellular production of adenosine is greatly enhanced in inflamed tissues, ischemic tissues and under hypoxia, where ATP is released from damaged cells. Much evidence has been accumulated on adenosine antinflammatory effects mediated through A 2A receptor activation; A2A adenosine receptor has also been shown to play a role in matrix deposition and wound healing in a damaged tissue, contributing to dermal tissue protection and repair...
December 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29212831/impaired-pulmonary-arterial-vasoconstriction-and-nitric-oxide-mediated-relaxation-underlie-severe-pulmonary-hypertension-in-sugen-hypoxia-rat-model
#5
Helen Christou, Hannes Hudalla, Zoe Michael, Evgenia Filatava, Jun Li, Minglin Zhu, Jose Possomato-Vieira, Carlos Dias-Junior, Stella Kourembanas, Raouf A Khalil
Pulmonary vasoreactivity could determine the responsiveness to vasodilators and in turn the prognosis of pulmonary hypertension (PH). We hypothesized that pulmonary vasoreactivity is impaired, and examined the underlying mechanisms, in the sugen-hypoxia rat model of severe PH. Male Sprague-Dawley rats were injected with sugen (20 mg/kg sc) and exposed to hypoxia (9% O2) for 3 weeks followed by 4 weeks in normoxia (Su/Hx), or treated with sugen alone (Su) or hypoxia alone (Hx) or neither (Nx). After hemodynamic measurements, the heart was assessed for right ventricular hypertrophy (Fulton's Index), the pulmonary artery, aorta and mesenteric arteries were isolated for vascular function studies, and contractile markers were measured in pulmonary artery using quantitative PCR...
December 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29203576/dimethoxy-etomidate-a-non-hypnotic-etomidate-analog-that-potently-inhibits-steroidogenesis
#6
Megan McGrath, Celena Ma, Douglas Raines
Cushing's syndrome is characterized by the overproduction of adrenocortical steroids. Steroidogenesis inhibitors are mainstays of medical therapy for Cushing's syndrome; unfortunately, adverse side effects and treatment failures are common with currently available drugs. The general anesthetic induction agent etomidate is among the most potent inhibitors of adrenocortical steroidogenesis. However, its use as a treatment for Cushing's syndrome is complicated by its sedative-hypnotic activity and ability to produce myoclonus, central nervous system actions thought to be mediated by the GABAA receptor...
December 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29203575/chronic-%C3%AE-9-thc-in-rhesus-monkeys-effects-on-cognitive-performance-and-dopamine-d2-d3-receptor-availability
#7
William S John, Thomas J Martin, Kiran K Solingapuram Sai, Susan H Nader, H D Gage, Akiva Mintz, Michael A Nader
Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of those deficits remain unclear. Adult male rhesus monkeys (N=6) responded in the mornings on tasks designed to assess different cognitive domains using CANTAB touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ9-tetrahydrocannabinol (THC; 0...
December 4, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29187590/selective-cannabinoid-2-receptor-stimulation-reduces-tubular-epithelial-cell-damage-following-renal-ischemia-reperfusion-injury
#8
Jeffrey D Pressly, Suni M Mustafa, Ammaar Abidi, Sahar Alghamdi, Pankaj Pandey, Kuldeep K Roy, Robert Doerksen, Bob M Moore, Frank Park
Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with increased rates of mortality. Currently, therapies to treat AKI are not available, so identification of new targets which, upon diagnosis of AKI, can be modulated to ameliorate renal damage is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295, was designed, synthesized, and tested in vitro and in silico. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI...
November 29, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29180359/tegoprazan-a-novel-potassium-competitive-acid-blocker-to-control-gastric-acid-secretion-and-motility
#9
Nobuyuki Takahashi, Yukinori Take
Tegoprazan, (S)-4-((5,7-difluorochroman-4-yl)oxy)-N,N,2-trimethyl-1H-benzo[d]imidazole-6-carboxamide, a potassium-competitive acid blocker (P-CAB), is a novel potent and highly selective inhibitor of gastric H+/K+-ATPase. Tegoprazan inhibited porcine, canine, and human H+/K+-ATPases in vitro with IC50 values ranging 0.29 ~ 0.52 μM while that for canine kidney Na+/K+-ATPase was more than 100 μM. A kinetic analysis revealed that tegoprazan inhibited H+/K+-ATPase with potassium-competitive manner and the binding was reversible...
November 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29180358/nonclinical-cardiovascular-studies-of-prucalopride-a-highly-selective-5-hydroxytryptamine-4-receptor-agonist
#10
Kelly Conlon, Joris H De Maeyer, Chris Bruce, Jan A J Schuurkes, Lee Christie, James McRedmond, Katayoun Derakhchan, Paul R Wade
Patients with chronic constipation benefit from treatment with 5-hydroxytryptamine 4 (5-HT4) receptor agonists. However, the first-generation 5-HT4 receptor agonists cisapride and tegaserod were withdrawn from the market owing to rare cardiovascular adverse events, which were not 5-HT4-receptor-related, but due to the lack of selectivity of these drugs. Here we report the nonclinical cardiovascular profile of the selective 5-HT4 receptor agonist prucalopride. To assess its non-5-HT4 receptor-mediated effects on cardiovascular electrophysiological parameters, in vitro studies were performed in human ether-a-go-go-related gene-transfected cells, guinea pig ventricular myocytes and papillary muscle preparations, rabbit and dog Purkinje fibers, and the Langendorff rabbit heart...
November 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29167350/safinamide-differentially-modulates-in-vivo-glutamate-and-gaba-release-in-the-rat-hippocampus-and-basal-ganglia
#11
Michele Morari, Alberto Brugnoli, Clarissa Anna Pisano, Salvatore Novello, Carla Caccia, Elsa Melloni, Gloria Padoani, Silvia Vailati, Marco Sardina
Safinamide has been recently approved as add-on to levodopa therapy in Parkinson's disease. In addition to inhibiting monoamine oxidase-type B, it also blocks sodium channels and modulates glutamate release in vitro. Since this property might contribute to the therapeutic action of the drug, we undertook the present study to investigate whether safinamide inhibits glutamate release also in vivo, and whether this effect is consistent across different brain areas and is selective for glutamatergic neurons. To this aim, in vivo microdialysis was used to monitor the spontaneous and veratridine-induced glutamate and GABA release in the hippocampus and basal ganglia of naive, awake rats...
November 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29162628/etiopathogenesis-and-pharmacological-prevention-of-a-type-2-diabetes-model-in-male-mice
#12
Alberto Loizzo, Santi M Spampinato, Gabriele Campana, Stefano Loizzo
We describe a stress-derived type-2 diabetes model in male mice, and formulate new hypotheses on how the model was induced, how diabetes-like alterations were prevented through specific pharmacological treatments, and how its possible neuroendocrine pathogenesis could be hypothesized. Pregnant females arrived in our laboratory on their 14th day of conceptional age. After birth, control mice never showed any apparent behavioral-metabolic-endocrine alterations. However, application of postnatal stress (brief mother deprivation, plus sham injection, daily from birth to weaning), was followed in adult male mice by two series of diabetes-like alterations...
November 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29162627/a-therapeutic-combination-of-gpcr-modulators-that-protects-photoreceptors-from-degeneration
#13
Tivadar Orban, Henri Leinonen, Tamar Getter, Zhiqian Dong, Wenyu Sun, Songqi Gao, Alexander Veenstra, Hossein Heidari-Torkabadi, Timothy S Kern, Philip D Kiser, Krzysztof Palczewski
Degeneration of retinal photoreceptor cells can arise from environmental and/or genetic causes. Since photoreceptor cells, the retinal pigment epithelium (RPE), neurons and glial cells of the retina are intimately associated; all cell types eventually are affected by retinal degenerative diseases. Such diseases often originate either in rod and/or cone photoreceptor cells or the RPE. Of these, cone cells located in the central retina are especially important for daily human activity. Here we describe the protection of cone cells by a combination therapy consisting of the G protein-coupled receptor modulators metoprolol, tamsulosin, and bromocriptine...
November 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29158210/longitudinal-influence-of-pregnancy-on-nicotine-metabolic-pathways
#14
Taraneh Taghavi, Christopher A Arger, Sarah H Heil, Stephen T Higgins, Rachel F Tyndale
Nicotine metabolism increases in pregnancy which may contribute to the difficulties that pregnant women have in quitting smoking. We aimed to determine the extent and timing of changes in nicotine metabolic pathways, including C-oxidation, N-glucuronidation, and the pregnancy-induced influences on the activity of enzymes mediating these pathways (CYP2A6 and UGT2B10, respectively). Current smoking pregnant women (n=47) provided a urine sample during early pregnancy (12.5 weeks), late pregnancy (28.9 weeks), and 6 months postpartum...
November 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29142081/genetic-and-molecular-regulation-of-extrasynaptic-gaba-a-receptors-in-the-brain-therapeutic-insights-for-epilepsy
#15
Shu-Hui Chuang, Doodipala Samba Reddy
GABA-A receptors play a pivotal role in many brain diseases. Epilepsy is caused by acquired conditions and genetic defects in GABA receptor channels regulating neuronal excitability in the brain. The latter is referred to as GABA channelopathies. In the last two decades, major advances have been made in the genetics of epilepsy. The presence of specific GABAergic genetic abnormalities leading to some of the classical epileptic syndromes has been identified. Advances in molecular cloning and recombinant systems have helped characterize mutations in GABA-A receptor subunit genes in clinical neurology...
November 15, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29133386/restoration-of-rostral-ventrolateral-medulla-cystathionine-%C3%AE-lyase-activity-underlies-moxonidine-evoked-neuroprotection-and-sympathoinhibition-in-diabetic-rats
#16
Mohamed A Fouda, Shaimaa S El-Sayed, Abdel A Abdel-Rahman
We recently demonstrated a fundamental role for cystathionine-γ lyase (CSE)-derived hydrogen sulfide (H2S) in the cardioprotective effect of the centrally acting drug moxonidine in diabetic rats. Whether a downregulated CSE/H2S system in the rostral ventrolateral medulla (RVLM) underlies neuronal oxidative stress and sympathoexcitation in diabetes has not been investigated. Along with addressing this question, we tested the hypothesis that moxonidine prevents the diabetes-evoked neurochemical effects by restoring CSE/H2S function within its major site of action, the RVLM...
November 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29127109/incb040093-is-a-novel-pi3k%C3%AE-inhibitor-for-the-treatment-of-b-cell-lymphoid-malignancies
#17
Niu Shin, Yun-Long Li, Song Mei, Kathy He Wang, Leslie Hall, Kamna Katiyar, Qian Wang, Gengjie Yang, Beth Rumberger, Lynn Leffet, Xin He, Mark Rupar, Kevin Bowman, Margaret Favata, Jun Li, Mike Liu, Yanlong Li, Maryanne Covington, Holly Koblish, Maxim Soloviev, Dana Shuey, Timothy Burn, Sharon Diamond, Jordan Fridman, Andrew Combs, Wenqing Yao, Swamy Yeleswaram, Gregory Hollis, Kris Vaddi, Reid Huber, Robert Newton, Peggy Scherle
PI3Kδ is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. INCB040093 is a novel PI3Kδ small molecule inhibitor and has demonstrated promising efficacy in patients with Hodgkin's lymphoma in clinical studies. Here, we disclose the chemical structure and the preclinical activity of the compound. In biochemical assays, INCB040093 potently inhibits the PI3Kδ kinase, with 74 to >900-fold selectivity against other PI3K family members...
November 10, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29118035/single-channel-analysis-of-isoflurane-and-ethanol-enhancement-of-taurine-activated-glycine-receptors
#18
Dean Kirson, Jelena Todorovic, S John Mihic
The amino acid taurine is an endogenous ligand acting on glycine receptors and is released by astrocytes in many brain regions, such as the nucleus accumbens and prefrontal cortex. Taurine is a partial agonist with an efficacy significantly lower than that of glycine. Allosteric modulators such as ethanol and isoflurane produce leftward shifts of glycine concentration-response curves but have no effects at saturating glycine concentrations. In contrast, in whole-cell electrophysiology studies these modulators increase the effects of saturating taurine concentrations...
November 8, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29101218/discovery-of-novel-small-molecule-inducers-of-heme-oxygenase-1-that-protect-human-ipsc-derived-cardiomyocytes-from-oxidative-stress
#19
R Jason Kirby, Daniela B Divlianska, Kanupriya Whig, Nadezda Bryan, Camilo J Morfa, Ada Koo, Becky L Hood, Kevin H Nguyen, Patrick Maloney, Satayamaheshwar Peddibhotla, E Hampton Sessions, Paul M Hershberger, Layton H Smith, Siobhan Malany
Oxidative injury to cardiomyocytes plays a critical role in cardiac pathogenesis following myocardial infarction. Transplantation of stem cell-derived cardiomyocytes has recently progressed as a novel treatment to repair damaged cardiac tissue but its efficacy has been limited by poor survival of transplanted cells due to oxidative stress in the post-transplantation environment. Identification of small molecules that activate cardioprotective pathways to prevent oxidative damage and increase survival of stem cells post-transplantation is therefore of great interest to improve the efficacy of stem cell therapies...
November 3, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29101217/epigenetic-histone-deacetylation-inhibition-prevents-the-development-and-persistence-of-temporal-lobe-epilepsy
#20
Sandesh D Reddy, Bryan C Clossen, Doodipala Samba Reddy
Epilepsy is a chronic brain disease characterized by repeated unprovoked seizures. Currently, no drug therapy exists for curing epilepsy or disease-modification in people at risk. Despite several emerging mechanisms, there have been few studies of epigenetic signaling in epileptogenesis, the process whereby a normal brain becomes progressively epileptic because of precipitating factors. Here, we report a novel role of histone deacetylation as critical epigenetic mechanism in epileptogenesis. Experiments were conducted using the histone deacetylase (HDAC) inhibitor sodium butyrate in the hippocampus kindling model of temporal lobe epilepsy (TLE), a classic model heavily used to approve drugs for treatment of epilepsy...
November 3, 2017: Journal of Pharmacology and Experimental Therapeutics
journal
journal
23880
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"