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https://www.readbyqxmd.com/read/28926841/beneficial-combination-of-lacosamide-with-retigabine-in-experimental-animals-an-isobolographic-analysis
#1
Jarogniew J Luszczki, Mirosław Zagaja, Barbara Miziak, Maria W Kondrat-Wrobel, Katarzyna Zaluska, Paula Wroblewska-Luczka, Piotr Adamczuk, Stanislaw J Czuczwar, Magdalena Florek-Luszczki
BACKGROUND/AIM: To isobolographically determine the types of interactions that occur between retigabine and lacosamide (LCM; two third-generation antiepileptic drugs) with respect to their anticonvulsant activity and acute adverse effects (sedation) in the maximal electroshock-induced seizures (MES) and chimney test (motor performance) in adult male Swiss mice. METHODS: Type I isobolographic analysis for nonparallel dose-response effects for the combination of retigabine with LCM (at the fixed-ratio of 1:1) in both the MES and chimney test in mice was performed...
September 20, 2017: Pharmacology
https://www.readbyqxmd.com/read/28918457/effects-of-menthol-and-its-interaction-with-nicotine-conditioned-cue-on-nicotine-seeking-behavior-in-rats
#2
Erin Harrison, Lisa Biswas, Ramachandram Avusula, Meiyu Zhang, Yongzhen Gong, Xiu Liu
RATIONALE: Increasing clinical evidence suggests that menthol, a significant flavoring additive in tobacco products, may contribute to smoking and nicotine dependence. Relapse to smoking behavior presents a formidable challenge for the treatment of tobacco addiction. An unresolved issue is whether the mentholation of tobacco products precipitates relapse to tobacco use in abstinent smokers. OBJECTIVES: The present study examined the effects of menthol on the perseverance and relapse of nicotine-seeking behavior in rats...
September 16, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28916995/effects-of-environmental-enrichment-on-self-administration-of-the-short-acting-opioid-remifentanil-in-male-rats
#3
Rebecca S Hofford, Jonathan J Chow, Joshua S Beckmann, Michael T Bardo
BACKGROUND: Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil...
September 15, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28889212/cocaine-like-discriminative-stimulus-effects-of-norepinephrine-preferring-monoamine-releasers-time-course-and-interaction-studies-in-rhesus-monkeys
#4
Stephen J Kohut, David S Jacobs, Richard B Rothman, John S Partilla, Jack Bergman, Bruce E Blough
RATIONALE: The therapeutic potential of monoamine releasers with prominent dopaminergic effects is hindered by their high abuse liability. OBJECTIVES: The present study examined the effects of several novel "norepinephrine (NE)-preferring" monoamine releasers relative to non-selective monoamine releasers, d-amphetamine and d-methamphetamine, in rhesus monkeys trained to discriminate cocaine. NE-preferring releasers were approximately 13-fold more potent for NE compared to dopamine release and ranged in potency for serotonin release (PAL-329 < l-methamphetamine < PAL-169)...
September 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28885457/cannabis-constituent-synergy-in-a-mouse-neuropathic-pain-model
#5
Sherelle L Casey, Nicholas Atwal, Christopher W Vaughan
Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28885007/stereoselective-differences-between-the-reinforcing-and-motivational-effects-of-cathinone-derived-4-methylmethcathinone-mephedrone-in-self-administering-rats
#6
Helene L Philogene-Khalid, Steven J Simmons, Sunil Nayak, Rose M Martorana, Shu H Su, Yohanka Caro, Brona Ranieri, Kathryn DiFurio, Lili Mo, Taylor A Gentile, Ali Murad, Allen B Reitz, John W Muschamp, Scott M Rawls
Mephedrone (4-methylmethcathinone (4-MMC)) (MEPH) is a new psychoactive substance (NPS) of the synthetic cathinone class. MEPH has a chiral center and exists as two enantiomers (R-,S-MEPH), yet stereospecific effects of MEPH have not been extensively investigated in preclinical assays. Because significant behavioral and neurochemical differences can exist between enantiomers, probing effects of stereochemistry on biological activity enables separation of adverse and therapeutic effects. Our prior work showed that R-MEPH, relative to S-MEPH, produced greater locomotor activation, place preference and facilitation of brain reward thresholds in rodents...
September 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28882561/locomotor-and-reinforcing-effects-of-pentedrone-pentylone-and-methylone-in-rats
#7
Mehrak Javadi-Paydar, Jacques D Nguyen, Sophia A Vandewater, Tobin J Dickerson, Michael A Taffe
The broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the α-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), α-pyrrolidinopentiophenone (α-PVP)) but not in the monoamine releasers (mephedrone, methylone)...
September 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28870526/drug-repurposing-strategy-against-trypanosoma-cruzi-infection-in-vitro-and-in-vivo-assessment-of-the-activity-of-metronidazole-in-mono-and-combined-therapy
#8
M R Simões-Silva, J S De Araújo, G M Oliveira, K C Demarque, R B Peres, I D'Almeida-Melo, D G J Batista, C F Da Silva, C Cardoso-Santos, P B Da Silva, M M Batista, M T Bahia, M N C Soeiro
Metronidazole (Mtz) is a commercial broad-spectrum nitroimidazolic derivative with relevant antimicrobial activity and relative safety profile. Therefore, it is fair to consider Mtz a candidate for drug repurposing for other neglected conditions such as Chagas disease (CD), a parasitic pathology caused by Trypanosoma cruzi. CD is treated only with benznidazole (Bz) and nifurtimox, both introduced in clinics decades ago despite important limitations, including low efficacy on the later disease stage (chronic form) and severe side effects...
September 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28870523/antagonism-of-mglu2-3-receptors-in-the-nucleus-accumbens-prevents-oxytocin-from-reducing-cued-methamphetamine-seeking-in-male-and-female-rats
#9
Aurelien Bernheim, Kah-Chung Leong, Carole Berini, Carmela M Reichel
Methamphetamine (meth) addiction is a prevalent health concern worldwide, yet remains without approved pharmacological treatments. Preclinical evidence suggests that oxytocin may decrease relapse, but the neuronal underpinnings driving this effect remain unknown. Here we investigate whether oxytocin's effect is dependent on presynaptic glutamatergic regulation in the nucleus accumbens core (NAcore) by blocking metabotropic glutamate receptors 2/3 (mGluR2/3). Male and female Sprague-Dawley rats self-administered meth or sucrose on an escalating fixed ratio, followed by extinction and cue-induced reinstatement sessions...
September 1, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28863965/-utility-of-normality-low-limit-of-spirometry-in-diagnosed-copd-patients
#10
J C Naveiro-Rilo, S García García, L Flores-Zurutuza, L Carazo Fernández, C Domínguez Fernández, J L Palomo García
AIM: To evaluate the differences in COPD patients below the lower limit of normal (LLN) of the fixed ratio FEV1/FVC < 0.70 and those above this limit. PATIENTS AND METHODS: Cross-sectional study. COPD patients between 40 and 85 years old included in primary care clinical record database were randomly selected. Baseline and postbronchodilator spirometries were performed. Two groups of patients were established: FEV1/FVC<0.70 and ≤LIN (group1) and FEV/FVC<0...
August 29, 2017: Revista de Calidad Asistencial: Organo de la Sociedad Española de Calidad Asistencial
https://www.readbyqxmd.com/read/28862799/initiating-therapy-in-patients-newly-diagnosed-with-type-2-diabetes-combination-therapy-versus-a-stepwise-approach
#11
REVIEW
Eugenio Cersosimo, Eric L Johnson, Christina Chovanes, Neil Skolnik
There is clear evidence that achieving glycaemic targets reduces the risk of developing complications as a result of type 2 diabetes (T2D). Many patients, however, continue to have suboptimal glycaemic control due to issues that include unclear advice on how to achieve these targets as well as clinical inertia. The two management approaches recommended for patients newly diagnosed with T2D are stepwise and combination therapy, each of which has advantages and disadvantages. Stepwise therapy may result in good patient adherence and allow greater individualization of therapy, minimization of side effects, and cost, and so may be appropriate for patients who are closer to goal...
September 1, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28857460/working-memory-and-salivary-brain-derived-neurotrophic-factor-as-developmental-predictors-of-cocaine-seeking-in-male-and-female-rats
#12
Chloe J Jordan, Susan L Andersen
Poor working memory is linked to future risk-taking behaviors. Lifelong risk of habitual drug use is highest in individuals who initiate use in early adolescence. We sought to determine in rats whether juvenile traits, specifically poor working memory and low salivary brain-derived neurotrophic factor (BDNF), are related to elevated cocaine taking and relapse in adolescence and adulthood. On postnatal day (P) 20, working memory was assessed using the novel object recognition task in male and female rats. Saliva was assayed at P20 for BDNF before cocaine self-administration on P28 [0...
August 31, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28832319/uncertainty-exposure-causes-behavioural-sensitization-and-increases-risky-decision-making-in-male-rats-toward-modelling-gambling-disorder
#13
Fiona D Zeeb, Zhaoxia Li, Daniel C Fisher, Martin H Zack, Paul J Fletcher
BACKGROUND: An animal model of gambling disorder, previously known as pathological gambling, could advance our understanding of the disorder and help with treatment development. We hypothesized that repeated exposure to uncertainty during gambling induces behavioural and dopamine (DA) sensitization - similar to chronic exposure to drugs of abuse. Uncertainty exposure (UE) may also increase risky decision-making in an animal model of gambling disorder. METHODS: Male Sprague Dawley rats received 56 UE sessions, during which animals responded for saccharin according to an unpredictable, variable ratio schedule of reinforcement (VR group)...
August 23, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/28822051/new-basal-insulins-a-clinical-perspective-of-their-use-in-the-treatment-of-type-2-diabetes-and-novel-treatment-options-beyond-basal-insulin
#14
REVIEW
Patrick F Frias, Juan Pablo Frias
PURPOSE OF REVIEW: The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy. RECENT FINDINGS: Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity...
August 18, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28811192/relative-reinforcing-effects-of-second-generation-synthetic-cathinones-acquisition-of-self-administration-and-fixed-ratio-dose-response-curves-in-rats
#15
REVIEW
Brenda M Gannon, Kayla I Galindo, Melson P Mesmin, Agnieszka Sulima, Kenner C Rice, Gregory T Collins
"Bath salts" preparations contain synthetic cathinones which interact with monoamine transporters and function as either monoamine uptake inhibitors or releasers. 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), and 4-methylmethcathinone (mephedrone) were three of the most common cathinones (i.e., "first-generation" cathinones); however, after the US Drug Enforcement Administration placed them under Schedule I regulations, they were replaced with structurally related cathinones that were not subject to regulations (i...
August 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28771757/supra-additive-interaction-of-docosahexaenoic-acid-and-naproxen-and-gastric-safety-on-the-formalin-test-in-rats
#16
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/28771656/transfusion-practice-in-trauma-resuscitation
#17
REVIEW
Ashley M Eckel, John R Hess
Recognition of the acute coagulopathy of trauma and the limits of reconstituting whole blood with conventional blood components has led to a radical change in the way trauma patients with severe injuries are resuscitated. Massive transfusion protocols (MTP) have evolved toward the administration of conventional blood components in fixed ratios. Administration of a 1:1:1 unit ratio of fresh frozen plasma to whole-blood-derived platelets to packed red blood cells is now the most common strategy and the stated goal of directors of >80% of the level I trauma centers in the United States...
August 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28749428/cannabinoid-receptor-1-and-fatty-acid-amide-hydrolase-contribute-to-operant-sensation-seeking-in-mice
#18
Alexander I Helfand, Christopher M Olsen, Cecilia J Hillard
A large body of evidence in humans and preclinical models supports a role for the endocannabinoid system in the proper execution of motivated or goal-directed behaviors. Operant sensation seeking (OSS) is a task that uses varied sensory stimuli as a reinforcer to maintain operant responding in mice. The purpose of the studies in this report was to begin to explore the role of endocannabinoid signaling in OSS utilizing cannabinoid receptor 1 (CB1R) and fatty acid amide hydrolase (FAAH) knock out mice. Compared to wild type littermate controls, CB1R knock out mice exhibited significantly fewer active responses and earned significantly fewer reinforcers in fixed ratio and progressive ratio schedules...
July 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28741967/iglarlixi-a-titratable-once-daily-fixed-ratio-combination-of-basal-insulin-and-lixisenatide-for-intensifying-type-2-diabetes-management-for-patients-inadequately-controlled-on-basal-insulin-with-or-without-oral-agents
#19
Neil Skolnik, Renell S Dupree, Eric L Johnson
BACKGROUND: Achieving and maintaining glycemic control is important for people with type 2 diabetes (T2D) in order to reduce disease-related complications and mortality; however, about half of US patients fail to meet glycemic targets. iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide for once-daily administration, was recently approved by the US Food and Drug Administration for use in adults with T2D inadequately controlled on basal insulin (<60 U daily) or lixisenatide...
July 25, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28736104/opioid-induced-constipation-relief-of-fixed-ratio-combination-prolonged-release-oxycodone-naloxone-compared-with-oxycodone-and-morphine-for-chronic-non-malignant-pain-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#20
REVIEW
Lang Huang, Jian-Guo Zhou, Yu Zhang, Fei Wang, Yi Wang, Da-Hai Liu, Xin-Juan Li, Shui-Ping Lv, Su-Han Jin, Yu-Ju Bai, Hu Ma
BACKGROUND: Opioid-induced constipation (OIC) is one of the most frequent and severe adverse events (AEs) following treatment with opioids. Recent studies have indicated that fixed-ratio combination prolonged-release oxycodone/naloxone (OXN PR) could decrease OIC with similar pain relief compared with other opioids. OBJECTIVES: We systematically reviewed (PROSPERO registration numbers: CRD42016036244) the constipation relief of OXN PR compared with other opioids regardless of formulation, prolonged-release or extended-release used for the relief of chronic pain...
July 20, 2017: Journal of Pain and Symptom Management
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