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Drug Development Research

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https://www.readbyqxmd.com/read/28940250/synergistic-interaction-of-a-gabapentin-mangiferin-combination-in-formalin-induced-secondary-mechanical-allodynia-and-hyperalgesia-in-rats-is-mediated-by-activation-of-no-cyclic-gmp-atp-sensitive-k-channel-pathway
#1
Beatriz Godínez-Chaparro, Geovanna Nallely Quiñonez-Bastidas, Isabel Rocío Rojas-Hernández, Amaya Montserrat Austrich-Olivares, Alfonso Mata-Bermudez
Preclinical Research Gabapentin is an anticonvulsant used to treat neuropathic pain. Mangiferin is an antioxidant that has antinociceptive and antiallodynic effects in inflammatory and neuropathic pain models. The purpose of this study was to determine the interaction between mangiferin and gabapentin in the development and maintenance of formalin-induced secondary allodynia and hyperalgesia in rats. Gabapentin, mangiferin, or their fixed-dose ratio combination were administrated peripherally. Isobolographic analyses was used to define the nature of the interaction of antiallodynic and/or antihyperalgesic effects of the two compounds...
September 20, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28921601/is-2-hydroxypropyl-%C3%AE-cyclodextrin-a-suitable-carrier-for-central-administration-of-%C3%AE-9-tetrahydrocannabinol-preclinical-evidence
#2
R Agabio, F Sanna, C Lobina, M Monduzzi, V Nairi, F Cugia, S Mameli, G M Pisanu, G L Gessa, M R Melis
Preclinical Research Δ(9) -Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPβCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPβCD (30 and 135 μg of THC per animal) and vehicle were administered to Wistar rats...
September 18, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28921725/coenzyme-q10-prevents-the-interleukin-1-beta-induced-inflammatory-response-via-inhibition-of-mapk-signaling-pathways-in-rat-articular-chondrocytes
#3
Xing Li, Yuanqing Guo, Shuai Huang, Minhui He, Qiaoli Liu, Weizhi Chen, Minghao Liu, Dongliang Xu, Peiheng He
Preclinical Research Osteoarthritis (OA) is a widely prevalent degenerative joint disease that severely impairs the health of the elderly population resulting in a heavy economic burden worldwide. Coenzyme Q10 (CoQ10) has shown anti-inflammatory effects in some diseases. The present study aimed to investigate if CoQ10 would suppress catabolic responses of interleukin (IL)-1β-induced chondrocytes. Rat chondrocytes were cultured and pretreated with CoQ10, and then stimulated with or without IL-1β (10 ng/ml)...
September 17, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28921671/methyl-jasmonate-ameliorates-unpredictable-chronic-mild-stress-induced-behavioral-and-biochemical-alterations-in-mouse-brain
#4
Adaeze Adebesin, Abayomi M Ajayi, Elizabeth O Olonode, Osarume Omorogbe, Solomon Umukoro
Preclinical Research The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed...
September 17, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28875546/limiting-assumptions-in-the-design-of-peptidomimetics
#5
Garland R Marshall, Flavio Ballante
Preclinical Research Limiting the flexibility of organic compounds to enhance their affinity and selectivity for targeting a macromolecule involved in molecular recognition has become a well-developed paradigm in medicinal chemistry. While the role of reverse-turn motifs as peptidomimetics has received the most attention, β-sheets and helices are also important motifs for protein/protein interactions. The more complicated problem of mimicking the interacting surface of noncontiguous epitopes will not be considered in this review...
September 6, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28868795/ultra-low-doses-of-naltrexone-enhance-the-antiallodynic-effect-of-pregabalin-or-gabapentin-in-neuropathic-rats
#6
Jorge B Pineda-Farias, Nadia L Caram-Salas, Ana B Salinas-Abarca, Jorge Ocampo, Vinicio Granados-Soto
Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats...
September 3, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28833328/peptide-mimetics-fast-forward-look
#7
EDITORIAL
David Gurwitz
No abstract text is available yet for this article.
August 17, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28815721/rgd-peptide-based-target-drug-delivery-of-doxorubicin-nanomedicine
#8
Yuan Sun, Chen Kang, Fei Liu, You Zhou, Lei Luo, Hongzhi Qiao
Preclinical Research Doxorubicin (DOX) is commonly used for the treatment of breast cancer and lymphoma. However, its clinical use has been severely limited due to cardiotoxicity, requiring the development of safer and more efficient pharmaceutical formulations of DOX. Advances in nanotechnology have provided new ways to administer chemotherapeutic drugs like DOX are conveyed into the body and to tumor sites. These Nanotechnology approaches have aided in the selective accumulation of DOX into tumor sites via the enhanced permeability and retention...
August 16, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28815651/peptide-mimetic-drugs-for-modulating-thrombosis-and-hemostasis
#9
Kimberly Nellenbach, Ashley C Brown
Preclinical Research Hemostasis is the complex physiological process that stems bleeding at an injury site while simultaneously maintaining unobstructed circulation in other areas of the body. This system is kept in balance with finely tuned regulation by pro- and antithrombotic agents. When this balance is thrown out of equilibrium, uncontrolled bleeding, or thrombotic complications can occur. Because of the high number of hemostatic disorders, researchers are continually searching for improved technologies for controlling coagulation...
August 16, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28804913/on-bh3-mimetics-and-ca-2-signaling
#10
Pawel E Ferdek, Monika A Jakubowska
Preclinical Research BH3 mimetics are anticancer agents that reproduce the spatial arrangement of the BH3 domain of Bcl-2 family proteins. Just like the BH3-only proteins, these compounds bind to the hydrophobic cleft of the pro-survival Bcl-2 members such as Bcl-2 or Bcl-xL, and disrupt their heterodimerization with pro-apoptotic Bax or Bak, sensitizing cells to chemotherapy. In recent years, it has become clear that Bcl-2 family proteins are engaged in regulation of intracellular Ca(2+) homeostasis, including Ca(2+) release from the intracellular stores as well as Ca(2+) fluxes across the plasma membrane...
August 13, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28799168/small-scaffolds-big-potential-developing-miniature-proteins-as-therapeutic-agents
#11
Justin M Holub
Preclinical Research Miniature proteins are a class of oligopeptide characterized by their short sequence lengths and ability to adopt well-folded, three-dimensional structures. Because of their biomimetic nature and synthetic tractability, miniature proteins have been used to study a range of biochemical processes including fast protein folding, signal transduction, catalysis and molecular transport. Recently, miniature proteins have been gaining traction as potential therapeutic agents because their small size and ability to fold into defined tertiary structures facilitates their development as protein-based drugs...
August 10, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28786182/recent-advances-on-bioactive-constituents-in-ferula
#12
Yueting Zhou, Fang Xin, Guoqiang Zhang, Hexiang Qu, Desong Yang, Xiaoqiang Han
Preclinical Research The genus Ferula (Umbelliferea) is widely distributed across Central Asia and the Mediterranean. Some plants of the genus Ferula have been used as sources of pharmaceuticals for centuries. Ferula is a rich source of biologically active compounds, including coumarin derivatives, sesquiterpene-substituted compounds, daucane esters, humulane, and germacrane compounds, aromatic lactones and disulfide compounds. Therefore, utilizing these bioactive constituents with antimicrobial and insecticidal effects not only can provide a new strategy for developing drug and green pesticide, but also protect endangered plant resources...
August 8, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28776721/synergistic-interaction-of-matricaria-chamomilla-extract-with-diclofenac-and-indomethacin-on-carrageenan-induced-paw-inflammation-in-rats
#13
Mario I Ortiz, Raquel Cariño-Cortés, Héctor A Ponce-Monter, Martha P González-García, Gilberto Castañeda-Hernández, Mireya Salinas-Caballero
Preclinical Research The coadministration of non-steroidal anti-inflammatory drugs (NSAIDs) with medicinal plant extracts may increase anti-inflammatory activity, thus permitting the use of lower NSAID doses and limiting the side effects. The aim of this study was to explore the interactions between an ethanolic extract of M. chamomilla extract (MCE) with two NSAIDs, diclofenac and indomethacin on carrageenan-induced paw inflammation and gastric injury in rats. Diclofenac, indomethacin and MCE, or combinations with MCE produced an anti-inflammatory effect...
August 4, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28771761/metformin-protects-against-experimental-acrylamide-neuropathy-in-rats
#14
Samah S Oda
Preclinical Research To investigate the potential neuroprotective effects of metformin against experimental acrylamide neuropathy in rats, 24 rats were distributed into four equal groups (6 each). Group 1 was kept as a control. Group 2 (MET) was orally given metformin (200 mg/kg BW/day). Group 3 (ACR) was injected IP with acrylamide (50 mg/kg BW/day). Animals in group 4 (ACR + MET) were administered both MET and ACR at the same dose and route used in groups 2 and 3. Treatments were administered three times a week for three weeks...
August 3, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28771757/supra-additive-interaction-of-docosahexaenoic-acid-and-naproxen-and-gastric-safety-on-the-formalin-test-in-rats
#15
Arlette Guadalupe Arroyo-Lira, Fernando Rodríguez-Ramos, Mario I Ortiz, Gilberto Castañeda-Hernández, Aracely Evangelina Chávez-Piña
Preclinical Research The aim of this work was to evaluate the effect of docosahexaenoic acid (DHA) on the pharmacokinetics and pharmacodynamics-nociception-of naproxen in rats, as well as to determine the gastric safety resulting from this combination versus naproxen alone. Female Wistar rats were orally administered DHA, naproxen or the DHA-naproxen mixture at fixed-ratio combination of 1:3. The antinociceptive effect was evaluated using the formalin test. The gastric injury was determined 3 h after naproxen administration...
August 3, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28736996/phytochemical-investigation-antitumor-activity-and-hepatoprotective-effects-of-acrocarpus-fraxinifolius-leaf-extract
#16
Heba A S El-Nashar, Omayma A Eldahshan, Omama E Elshawi, Abdel Nasser B Singab
Preclinical Research Nine known phenolic compounds were isolated from an aqueous methanolic extract of Acrocarpus fraxinifolius Weight and Arn leaves (AFL) family Fabaceae. This extract of AFL contained approximately 169 mg gallic acid/g as assessed by HPLC. The AFL extract had marginal antitumor activity (IC50  > 200 µL/mL) but showed a concentration-dependent hepatoprotective effect against CCl4 -induced hepatotoxicity in vitro. Cell viability was increased, ALT and AST activity declined and reduced GSH concentration and SOD activity were restored as compared with silymarin...
July 24, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28736839/the-neurotensin-nts1-receptor-agonist-pd149163-produces-antidepressant-like-effects-in-the-forced-swim-test-further-support-for-neurotensin-as-a-novel-pharmacologic-strategy-for-antidepressant-drugs
#17
Lawrence M Carey, Remington J Rice, Adam J Prus
Preclinical Research Neurotensin is a nonbrain penetrant neuropeptide neurotransmitter that alters dopaminergic and serotonergic neurotransmission. Previous animal behavioral studies have demonstrated that intra-ventral tegmental administration of neurotensin and system administration of the selective neurotensin NTS1 receptor agonist, PD149163 produce antidepressant-like effects in a forced swim test and a differential reinforcement of low rate task, respectively. The present study sought to expand upon these past findings by assessing systemic administration of PD149163 in a forced swim test, a primary antidepressant preclinical screening model, in mice...
July 24, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28736816/antinociceptive-activity-of-ent-dihydrotucumanoic-acid-isolated-from-gymnosperma-glutinosum-spreng-less
#18
Angel Josabad Alonso-Castro, Marco Martin González-Chávez, Juan Ramón Zapata-Morales, Alexia Karina Verdinez-Portales, Amanda Sánchez-Recillas, Rolffy Ortiz-Andrade, Mario Isiordia-Espinoza, Fidel Martínez-Gutiérrez, Marco Antonio Ramírez-Morales, Fabiola Domínguez, María Elizabeth Juache-Flores, Roberto Martínez
Preclinical Research The diterpene ent-dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1-250 µM), and the antibacterial (50-1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1-100 mg/kg p.o.) and anti-inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12-O-tetradecanoylphorbol-13-acetate, respectively...
July 24, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28718949/high-dosage-of-vitamin-d-regulates-the-energy-metabolism-and-increases-insulin-sensitivity-but-are-associated-with-high-levels-of-kidney-damage
#19
Rafael Calais Gaspar, José Diego Botezelli, Gabriel Keine Kuga, Vitor Rosetto Muñoz, Andressa Coope, Rodrigo Martins Pereira, Adelino Sanchez Ramos da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle, José Rodrigo Pauli
Preclinical Research Metabolic disorders are responsible for more than 60% of all deaths worldwide. Calcitriol or vitamin D (vitD) deficiency is associated with a large proportion of these diseases is an important therapeutic target for exploration. This study evaluated the administration of high doses of vitD (3000 IU/kg) in obese and insulin-resistant C57BL/6J mice. Our results demonstrated that although high doses of vitD provided metabolic benefits such as increased insulin sensitivity and decreased body mass, this was associated with significant damage in the kidneys of obese mice...
July 18, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28786125/recent-advances-in-glp-1-receptor-agonists-for-use-in-diabetes-mellitus
#20
Dominic N McBrayer, Yftah Tal-Gan
Preclinical Research Mimetics of Glucagon-like peptide 1 (GLP-1) represent a useful alternative or complementary treatment choice to insulin in the treatment of diabetes mellitus. The lack of hypoglycemia as a side effect when GLP-1 receptor agonists are used along with the tendency of these therapeutic agents to prevent or even reduce weight gain makes them valuable targets in therapy development. However, native GLP-1 and many of its early analogues have very short half-lives, requiring repeated treatment to maintain therapeutic levels...
September 2017: Drug Development Research
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