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Marta Silva, José Tiago Costa-Pereira, Daniel Martins, Isaura Tavares
Diabetic neuropathy has a profound impact in the quality of life of patients who frequently complain of pain. The mechanisms underlying diabetic neuropathic pain (DNP) are no longer ascribed only to damage of peripheral nerves. The effects of diabetes at the central nervous system are currently considered causes of DPN. Management of DNP may be achieved by antidepressants that act on serotonin (5-HT) uptake, namely specific serotonin reuptake inhibitors. The rostroventromedial medulla (RVM) is a key pain control center involved in descending pain modulation at the spinal cord through local release of 5-HT and plays a peculiar role in the balance of bidirectional control (i...
October 4, 2016: Neurobiology of Disease
Ian Olver, Christina H Ruhlmann, Franziska Jahn, Lee Schwartzberg, Bernardo Rapoport, Cynthia N Rittenberg, Rebecca Clark-Snow
PURPOSE: The purpose of this review is to update the MASCC (Multinational Association of Supportive Care in Cancer) guidelines for controlling nausea and vomiting with chemotherapy of low or minimal emetic potential. METHODS: The antiemetic study group of MASCC met in Copenhagen in 2015 to review the MASCC antiemetic guidelines. A subgroup performed a systematic literature review on antiemetics for low emetogenic chemotherapy (LEC) and chemotherapy of minimal emetic potential and the chair presented the update recommendation to the whole group for discussion...
August 30, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Isabella Salzer, Enkhbileg Gantumur, Arsalan Yousuf, Stefan Boehm
Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron...
November 2016: Neuropharmacology
Fan Wang, Kaitlyn Knutson, Constanza Alcaino, David R Linden, Simon J Gibbons, Purna Kashyap, Madhusudan Grover, Richard Oeckler, Philip A Gottlieb, Hui Joyce Li, Andrew B Leiter, Gianrico Farrugia, Arthur Beyder
The enterochromaffin (EC) cell in GI epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine, 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The aim of this work was to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of small bowel...
July 9, 2016: Journal of Physiology
Karin Jordan, Richard Gralla, Giada Rizzi, Kimia Kashef
PURPOSE: Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO)...
November 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Yogita S Karandikar, Peeyush Belsare, Aditi Panditrao
OBJECTIVE: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. MATERIALS AND METHODS: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT1A Agonist) + PCT, and ondansetron (5HT3 antagonist) + PCT...
May 2016: Indian Journal of Pharmacology
Jérôme Tavernier, Mireille Jouannet-Romaszko, Helena Bertucat, Nathalie Marchiset, Mohum Bahadoor, Régine Chevrier
The anticancer drug technical commission (COTECH) of the Auvergne OMEDIT has set up a region-wide professional practice evaluation (PPE) with regards to antiemetic prescription practices in chemotherapy-induced nausea and vomiting (CINV), in order to evaluate their compliance with OMEDIT's guidelines. Are not included pediatric and hematologic protocols. A prospective survey was carried from November 2013 to January 2014 out in 14 medical centers in Auvergne. This clinical audit was based on the HAS (national healthcare authority) framework and used as a reference regional standards based on the MASCC Antiemetic Guidelines...
July 2016: Bulletin du Cancer
Sandro Barni, Fausto Petrelli, Mary Cabiddu
PURPOSE: Cardiac complications in cancer patients have been a significant medical problem in the last few years. Cardiosafety profile of most novel approved drugs, in cancer patients, is required by regulatory authorities. Risk of proarrhythmic effect associated with a new drug, in fact, is usually evaluated with specific studies conducted in agreement with ICHE14 guidelines. In this overview, we detailed the cardio safety profile of antiemetic drugs. In particular, we focused on data of 5HT3-RA drugs used for prevention of chemotherapy-induced nausea and vomiting in the oncology setting...
June 2016: Critical Reviews in Oncology/hematology
Isabel C Sumaya, Dee Bailey, Susan L Catlett
Investigation into the effects of a high-fat diet on depression in the context of 5-HT3 receptor function is important given 5-HT3 antagonism may represent a novel candidate for drug discovery. To more fully understand the relationship between the 5-HT3 receptor system, depression, and high-fat intake, our main interest was to study the short-term effects of a high-fat diet on the 5-HT3 receptor antagonist, ondansetron, and the 5-HT3 receptor agonist, 2-methyl-5-HT, as well as the SSRI, fluoxetine, in an animal model of depression...
May 2016: Pharmacology, Biochemistry, and Behavior
Deepali Gupta, Visakh Prabhakar, Mahesh Radhakrishnan
5HT3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists...
May 2016: Neuroscience and Biobehavioral Reviews
Alberto Salazar-Juárez, Susana Barbosa-Méndez, Noe Jurado, Ricardo Hernández-Miramontes, Philippe Leff, Benito Antón
Cocaine abuse is a major health problem worldwide. Treatment based on both 5-HT2A/C and 5-HT3 receptor antagonists attenuate not only the effects of cocaine abuse but also the incentive/motivational effect related to cocaine-paired cues. Mirtazapine, an antagonist of postsynaptic α2-adrenergic, 5-HT2A/C and 5HT3 receptors and inverse agonist of the 5-HT2C receptor, has been shown to effectively modify, at the preclinical and clinical levels, various behavioral alterations induced by drugs abuse. Therefore, it is important to assess whether chronic dosing of mirtazapine alters locomotor effects of cocaine as well as induction and expression of cocaine sensitization...
July 4, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Mohammad Nasehi
INTRODUCTION: The plethora of studies indicated that there is a cross talk relationship between harmaline and serotonergic (5-HT) system on cognitive and non-cognitive behaviors. Thus, the purpose of this study is to assess the effects of hippocampal 5-HT4 receptor on memory acquisition deficit induced by harmaline. METHODS: Harmaline was injected peritoneally, while 5-HT4 receptor agonist (RS67333) and antagonist (RS23597-190) were injected intra-hippocampal. A single-trial step-down passive avoidance, open field and tail flick tasks were used for measurement of memory, locomotor activity and pain responses, respectively...
July 2015: Basic and Clinical Neuroscience
Myung Ah Lee, Eun Kyung Cho, Sung Yong Oh, Joong Bae Ahn, Ji Yun Lee, Burke Thomas, Hun Jung, Jong Gwang Kim
Purpose: This study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian ChemoTherapy InduCed Emesis burden of illness (PrACTICE) study. Materials and Methods: This subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region...
February 12, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Nabil Adra, Costantine Albany, Mary J Brames, Somer Case-Eads, Cynthia S Johnson, Ziyue Liu, Christopher A Fausel, Timothy Breen, Nasser H Hanna, Ralph J Hauke, Joel Picus, Lawrence H Einhorn
PURPOSE: A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen...
July 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Akiko Hanai, Hiroshi Ishiguro, Takashi Sozu, Moe Tsuda, Hidenori Arai, Akira Mitani, Tadao Tsuboyama
Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group...
January 2016: Breast Cancer Research and Treatment
Joseph R Ruiz, Joe E Ensor, Jeffrey W Lim, Antoinette Van Meter, Thomas F Rahlfs
PURPOSE: Our practitioners are asked to consider a patient's postoperative nausea and vomiting (PONV) risk profile when developing their prophylactic antiemetic strategy. There is wide variation in employed strategies, and we have yet to determine the most effective PONV prophylactic regimen. The objective of this study is to compare prophylactic antiemetic regimens containing: phenothiazines to 5HT3 antagonists for effectiveness at reducing the incidence of Post-Anesthesia Care Unit (PACU) rescue antiemetic administration...
February 2015: Open Journal of Anesthesiology
Aziz Ouach, Frederic Pin, Emilie Bertrand, Johnny Vercouillie, Zuhal Gulhan, Céline Mothes, Jean-Bernard Deloye, Denis Guilloteau, Franck Suzenet, Sylvie Chalon, Sylvain Routier
We report here the synthesis of a large library of 1,2,3-triazole derivatives which were in vitro tested as α7 nAchR ligands. The SAR study revealed that several crucial factors are involved in the affinity of these compounds for α7 nAchR such as a (R) quinuclidine configuration and a mono C-3 quinuclidine substitution. The triazole ring was substituted by a phenyl ring bearing small OMe/CH2F groups or fluorine atom and by several heterocycles such as thiophenes, furanes, benzothiophenes or benzofuranes. Among the 30 derivatives tested, the two derivatives 10 and 39 with Ki in the nanomolar range were identified (2...
January 1, 2016: European Journal of Medicinal Chemistry
Nermeen A Eltahawy, Amany K Ibrahim, Mohamed M Radwan, Sawsan A Zaitone, Mohamed Gomaa, Mahmoud A ElSohly, Hashim A Hassanean, Safwat A Ahmed
Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of a new ceramide N-((2S,3R,4E,6E)-1,3-dihydroxyhenicosa-4,6-dien-2-yl)tridecanamide (1). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The anticonvulsant activity of the isolated ceramide was measured in vivo using the pentylenetetrazole (PTZ)-induced seizure model, where it successfully antagonized the lethality of pentylenetetrazole in mice...
December 15, 2015: Bioorganic & Medicinal Chemistry Letters
Catalina Ayala Corredor, Carolina Solís Castillo
INTRODUCTION: In liaison psychiatry it is possible to get an integral view of patient's treatment and needs, paying special attention to pharmacological interactions and contraindications. Some particular cases motivated the description, report and review about other possible applications of 5HT2A and 5HT3 antagonist, particularly Mirtazapine and Olanzapine, in hyperalgesia syndrome, tinnitus and Progressive Multifocal Leukoencephalopathy by JC virus. METHOD: Cases report...
March 2012: Revista Colombiana de Psiquiatría
Deepali Gupta, Devadoss Thangaraj, Mahesh Radhakrishnan
Despite the presence of a multitudinous pharmacotherapy, diabetes-induced depressive disorder remains undertreated. Evidence suggests that brain serotonergic deficits are associated with depressive-like behavior in diabetes and that 5HT3 receptor (5HT3R) antagonists have serotonergic facilitatory effects. This study examined the effects of a novel 5HT3R antagonist, 4i (N-(3-chloro-2-methylphenyl)quinoxalin-2-carboxamide), in diabetes-induced depressive phenotypes. Experimentally, (1) to evaluate the effects of 4i, mice with 8-weeks of diabetes (induced by streptozotocin, 200mg/kg, i...
January 15, 2016: Behavioural Brain Research
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