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https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#1
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28648406/n-2-morpholin-4-yl-ethyl-2-1naphthyloxy-acetamide-inhibits-the-chronic-constriction-injury-generated-hyperalgesia-via-the-antagonism-of-sigma-1-receptors
#2
Josué Vidal Espinosa-Juárez, Osmar Antonio Jaramillo-Morales, Gabriel Navarrete-Vázquez, Luis Alberto Melo Hernández, Myrna Déciga-Campos, Francisco Javier López-Muñoz
The most used therapeutic treatment to relieve neuropathic pain is that of neuromodulators such as anti-epileptics or anti-depressants; however, there are alternatives that may be potentially useful. The sigma-1 receptor is a therapeutic target that has shown favorable results at preclinical levels. The aim of this study was to evaluate the anti-hyperalgesic effect of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI) and compare it both a sigma-1 antagonist (BD-1063) and also Gabapentin, as well as determine its possible role as an antagonist of sigma-1 receptors...
June 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28644196/cebranopadol-a-novel-first-in-class-analgesic-drug-candidate-first-experience-in-patients-with-chronic-low-back-pain-in-a-randomized-clinical-trial
#3
Annette Christoph, Marie-Henriette Eerdekens, Maurits Kok, Gisela Volkers, Rainer Freynhagen
Chronic low back pain (LBP) is a common condition, usually with involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first Phase II, randomized, doubleblind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate to severe chronic LBP with and without neuropathic pain component...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28631870/thalamic-deep-brain-stimulation-for-neuropathic-pain-efficacy-at-three-years-follow-up
#4
Vasco Abreu, Rui Vaz, Virgínia Rebelo, Maria José Rosas, Clara Chamadoira, Martin J Gillies, Tipu Z Aziz, Erlick A C Pereira
OBJECT: Chronic neuropathic pain is estimated to affect 3-4.5% of the worldwide population, posing a serious burden to society. Deep Brain Stimulation (DBS) is already established for movement disorders and also used to treat some "off-label" conditions. However, DBS for the treatment of chronic, drug refractory, neuropathic pain, has shown variable outcomes with few studies performed in the last decade. Thus, this procedure has consensus approval in parts of Europe but not the USA. This study prospectively evaluated the efficacy at three years of DBS for neuropathic pain...
June 20, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28626478/comparative-effects-of-chronic-administrations-of-gabapentin-pregabalin-and-baclofen-on-rat-memory-using-object-recognition-test
#5
Asma Salimzade, Ali Hosseini-Sharifabad, Mohammad Rabbani
Memory impairment is one of the greatest concerns when it comes to long-term CNS-affecting drug administration. Drugs like gabapentin, pregabalin and baclofen are administered in a long-term period in conditions such as epilepsy, neuropathic pain, spasticity associated with spinal cord injury or multiple sclerosis. Despite their wide spread use, few data are available on the effects of these drugs on cognitive functions, such as learning memory. In the present study, the effects of long-term administration of gabapentin, pregabalin and baclofen on memory were investigated in a comparative manner...
June 2017: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28612120/anti-allodynic-action-of-the-disease-modifying-anti-rheumatic-drug-iguratimod-in-a-rat-model-of-neuropathic-pain
#6
K Morimoto, A Miura, Keiichi Tanaka
OBJECTIVE: Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study. METHODS: CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0)...
June 13, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28611661/discovery-and-development-of-calcium-channel-blockers
#7
REVIEW
Théophile Godfraind
In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28596150/pain-improvement-with-novel-combination-analgesic-regimens-pain-care-randomized-controlled-trial-protocol
#8
Ian Gilron, Dongsheng Tu, Ronald Holden, Alan C Jackson, Nader Ghasemlou, Scott Duggan, Elizabeth Vandenkerkhof, Roumen Milev
BACKGROUND: Neuropathic pain (NP) (including painful diabetic neuropathy, postherpetic neuralgia, etc) affects approximately 7% to 8% of the population and is associated with a devastating symptom burden as well as a profound economic impact for patients, their families, and the health care system. Current therapies have limited efficacy and dose-limiting adverse effects (AEs). Rational combination therapy with carefully selected NP drugs has shown potential for measurable improvements in pain relief, quality of life, and health care use...
June 8, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28593649/the-effect-of-gabapentin-and-tramadol-in-cancer-pain-induced-by-glioma-cell-in-rat-femur
#9
Janette Nallely Corona-Ramos, Myrna Déciga-Campos, Mario Romero-Piña, Luis A Medina, Issac Martínez-Racine, Osmar A Jaramillo-Morales, Patricia García-López, Francisco Javier López-Muñoz
Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (10(5) ) into the rat femur, by perforating the intercodiloid fossa...
June 7, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28578258/alternative-treatment-strategies-for-neuropathic-pain-role-of-indian-medicinal-plants-and-compounds-of-plant-origin-a-review
#10
REVIEW
Hasandeep Singh, Sakshi Bhushan, Rohit Arora, Harpal Singh Buttar, Saroj Arora, Balbir Singh
Neuropathic pain is a complex, chronic pain state accompanied by tissue injury and nerve damage. This important health issue constitutes a challenge for the modern medicine worldwide. The management of neuropathic pain remains a major clinical challenge, pertaining to an inadequate understanding of pathophysiological mechanisms of neuropathic pain. Various classes of drugs have been reported effective for the management of neuropathic pain viz. opiates, tricyclic antidepressants, and antiepileptic agents. However, association of adverse effects with these drugs hinders their confident prescription in people with neuropathic pain...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28573049/biphalin-a-dimeric-enkephalin-alleviates-lps-induced-activation-in-rat-primary-microglial-cultures-in-opioid-receptor-dependent-and-receptor-independent-manners
#11
Katarzyna Popiolek-Barczyk, Anna Piotrowska, Wioletta Makuch, Joanna Mika
Neuropathic pain is relatively less responsive to opioids than other types of pain, which is possibly due to a disrupted opioid system partially caused by the profound microglial cell activation that underlines neuroinflammation. We demonstrated that intrathecally injected biphalin, a dimeric enkephalin analog, diminished symptoms of neuropathy in a preclinical model of neuropathic pain in rats (CCI, chronic constriction injury of the sciatic nerve) at day 12 postinjury. Using primary microglial cell cultures, we revealed that biphalin did not influence cell viability but diminished NO production and expression of Iba1 in LPS-stimulated cells...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28570482/targeting-the-s1p-s1pr1-axis-mitigates-cancer-induced-bone-pain-and-neuroinflammation
#12
Shaness A Grenald, Timothy M Doyle, Hong Zhang, Lauren M Slosky, Zhoumou Chen, Tally M Largent-Milnes, Sarah Spiegel, Todd W Vanderah, Daniela Salvemini
Metastatic bone pain is the single most common form of cancer pain, and persists as a result of peripheral and central inflammatory, as well as, neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P)...
May 31, 2017: Pain
https://www.readbyqxmd.com/read/28557178/impact-of-etiology-and-duration-of-pain-on-pharmacological-treatment-effects-in-painful-polyneuropathy
#13
S H Sindrup, J Holbech, D Demant, N B Finnerup, F W Bach, T S Jensen
BACKGROUND: The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for. METHODS: We analysed data from four published, randomized, controlled trials of drugs in painful polyneuropathy to see if diabetic etiology and duration of neuropathic pain had an impact on drug efficacy...
May 30, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28554532/efficacy-of-venlafaxine-in-neuropathic-pain-a-narrative-review-of-optimized-treatment
#14
REVIEW
Anne-Priscille Trouvin, Serge Perrot, Célia Lloret-Linares
PURPOSE: The prevalence of neuropathic pain is high in the general population, and high priority is given to the management of this pain condition. The treatment of neuropathic pain remains challenging, despite the publication of national and international recommendations. The purpose of this narrative review of venlafaxine (VLX) is to provide a better knowledge of the pharmacology of this drug and a clearer view of its efficacy and tolerability in neuropathic pain. METHODS: Two independent reviewers searched PubMed with the following search terms: serotonin and noradrenalin reuptake inhibitors OR VLX hydrochloride AND pain...
June 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28554402/rebuilding-cns-inhibitory-circuits-to-control-chronic-neuropathic-pain-and-itch
#15
Joao M Braz, Alex Etlin, Dina Juarez-Salinas, Ida J Llewellyn-Smith, Allan I Basbaum
Cell transplantation offers an attractive alternative to pharmacotherapy for the management of a host of clinical conditions. Most importantly, the transplanted cells provide a continuous, local delivery of therapeutic compounds, which avoids many of the adverse side effects associated with systemically administered drugs. Here, we describe the broad therapeutic utility of transplanting precursors of cortical inhibitory interneurons derived from the embryonic medial ganglionic eminence (MGE), in a variety of chronic pain and itch models in the mouse...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552056/the-orexinergic-hypocretin-system-and-nociception-an-update-to-supraspinal-mechanisms
#16
Ali Roohbakhsh, Mohaddeseh Sadat Alavi, Hassan Azhdari Zarmehri
Chronic pain is a multifaceted and complex condition that is divided into somatic, visceral, and neuropathic pain. Although opioids and nonsteroidal anti-inflammatory drugs cause analgesia and are effective in the treatment of chronic pain, their utility is hampered by side effects, abuse potential, and development of tolerance to their pain-relieving effects. So, finding alternative analgesics with good efficacy and low side effects is of great interest and the orexinergic system is a potential candidate. Orexin-A and -B are exclusively expressed in the lateral hypothalamus and are involved in the feeding, sleep/wake cycle, cardiovascular function, hormone secretion, seizure, and pain modulation...
May 28, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28542026/combination-drug-therapy-of-pioglitazone-and-d-cycloserine-attenuates-chronic-orofacial-neuropathic-pain-and-anxiety-by-improving-mitochondrial-function-following-trigeminal-nerve-injury
#17
Danielle N Lyons, Liping Zhang, Jignesh D Pandya, Robert J Danaher, Fei Ma, Craig S Miller, Patrick G Sullivan, Cristian Sirbu, Karin N Westlund
OBJECTIVES: The study aim was to determine how peripheral trigeminal nerve injury affects mitochondrial respiration and to test efficacy of combined treatment with two FDA approved drugs with potential for improving mitochondrial bioenergetics, pain and anxiety related behaviors in a chronic orofacial neuropathic pain mouse model. METHODS: Efficacy of (R)-(+)-4-amino-3-isoxazolidinone (D-cycloserine, DCS), an NMDA antagonist/agonist, and Pioglitazone (PIO), a selective agonist of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was investigate in the trigeminal inflammatory compression (TIC) neuropathic nerve injury mouse model...
May 24, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28537441/characteristics-resource-utilization-and-safety-profile-of-patients-prescribed-with-neuropathic-pain-treatments-a-real-world-evidence-study-on-general-practices-in-europe-the-role-of-the-lidocaine-5-medicated-plaster
#18
Pablo Katz, Valeria Pegoraro, Hiltrud Liedgens
OBJECTIVES: To identify characteristics, resource utilization, and safety profile of patients prescribed with lidocaine 5% medicated plaster, pregabalin, gabapentin, amitriptyline and duloxetine when experiencing pain in the real-world setting of general practitioners (GPs) in Europe. METHODS: Retrospective analysis on real world data from IMS Health Longitudinal Patient Database. Patients with at least one prescription of the drugs of interest during 2014 were selected and those with a non-neuropathic pain-related diagnosis were excluded...
June 8, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28535116/is-mannitol-the-treatment-of-choice-for-patients-with-ciguatera-fish-poisoning
#19
Michael E Mullins, Robert S Hoffman
CONTEXT: Ciguatera fish poisoning arises primarily from consumption of carnivorous reef fish caught in tropical and sub-tropical waters. Ciguatoxins, a class of tasteless, heat-stable, polycyclic toxins produced by dinoflagellates, accumulate through the food chain and concentrate in various carnivorous fish, such as groupers, barracudas, wrasses, amberjack, kingfishes, and eels. Characteristics of ciguatera fish poisoning include early nausea, vomiting, and diarrhea in the first one to two days post ingestion, followed by the appearance of sensory disturbances...
May 23, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28530786/morphine-for-chronic-neuropathic-pain-in-adults
#20
REVIEW
Tess E Cooper, Junqiao Chen, Philip J Wiffen, Sheena Derry, Daniel B Carr, Dominic Aldington, Peter Cole, R Andrew Moore
BACKGROUND: Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain...
May 22, 2017: Cochrane Database of Systematic Reviews
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