keyword
MENU ▼
Read by QxMD icon Read
search

CGRP antagonists

keyword
https://www.readbyqxmd.com/read/28317098/cgrp-receptor-activity-in-mice-with-global-expression-of-human-receptor-activity-modifying-protein-1
#1
Keegan J Bohn, Baolin Li, Xiaofang Huang, Bianca N Mason, Anne-Sophie Wattiez, Adisa Kuburas, Christopher S Walker, Peiyi Yang, Jianliang Yu, Beverly A Heinz, Kirk W Johnson, Andrew F Russo
BACKGROUND AND PURPOSE: CGRP is a potent vasodilator and nociceptive neuropeptide linked to migraine. CGRP receptors are heterodimers of receptor activity-modifying protein-1 (RAMP1) and either calcitonin receptor-like receptor (CLR), which forms the canonical CGRP receptor, or calcitonin receptor (CTR), which forms the amylin-1 (AMY1 ) receptor. The goal of this study was to test whether transgenic mice globally expressing human RAMP1 (hRAMP1) have increased CGRP receptor activity and whether the receptors are sensitive to the human selective antagonist telcagepant...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28306261/asymmetric-synthesis-of-the-major-metabolite-of-a-cgrp-receptor-antagonist-and-mechanism-of-epoxide-hydrogenolysis
#2
Guanglin Luo, Ling Chen, Charles M Conway, Walter Kostich, Benjamin M Johnson, Alicia Ng, John E Macor, Gene M Dubowchik
An asymmetric synthesis of the major metabolite of the CGRP recepotor antagonist BMS-846372 is presented. The variously substituted cyclohepta[b]pyridine ring system represents an under-explored ring system, and showed some unexpected chemistry. Reactivities of epoxide and ketone functional groups on cycloheptane ring were greatly controlled by a remote bulky TIPS group. The rate difference of the hydrogenolysis between two diastereomeric epoxide intermediates shed some light on the mechanism of epoxide hydrogenolysis, and further deuterium labeling studies unravelled more mechanistic details on this well known chemical transformation for the first time...
March 17, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28254863/bone-pain-induced-by-multiple-myeloma-is-reduced-by-targeting-v-atpase-and-asic3
#3
Masahiro Hiasa, Tatsuo Okui, Yohance M Allette, Matthew S Ripsch, Ge-Hong Sun-Wada, Hiroki Wakabayashi, G David Roodman, Fletcher A White, Toshiyuki Yoneda
Multiple myeloma patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model that employs JJN3 human multiple myeloma cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP(+)) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28205139/the-potentiating-effect-of-calcitonin-gene-related-peptide-on-transient-receptor-potential-vanilloid-1-activity-and-the-electrophysiological-responses-of-rat-trigeminal-neurons-to-nociceptive-stimuli
#4
Duangthip Chatchaisak, Mark Connor, Anan Srikiatkhachorn, Banthit Chetsawang
Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP...
February 15, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28192258/binding-and-functional-pharmacological-characteristics-of-gepant-type-antagonists-in-rat-brain-and-mesenteric-arteries
#5
Majid Sheykhzade, Nilofar Amandi, Monica Vidal Pla, Bahareh Abdolalizadeh, Anette Sams, Karin Warfvinge, Lars Edvinsson, Darryl S Pickering
AIM: The neuropeptide calcitonin gene-related peptide (CGRP) is found in afferent sensory nerve fibers innervating the resistance arteries and plays a pivotal role in a number of neurovascular diseases such as migraine and subarachnoid bleedings. The present study investigates the binding and antagonistic characteristics of small non-peptide CGRP receptor antagonists (i.e. gepants) in isolated rat brain and mesenteric resistance arteries. METHODS: The antagonistic behavior of gepants was investigated in isolated rat mesenteric arteries using a wire myograph setup while binding of gepants to CGRP receptors was investigated in rat brain membranes using a radioligand competitive binding assay...
March 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/28179394/pathophysiology-of-migraine-a-disorder-of-sensory-processing
#6
REVIEW
Peter J Goadsby, Philip R Holland, Margarida Martins-Oliveira, Jan Hoffmann, Christoph Schankin, Simon Akerman
Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28179153/activation-of-npffr2-leads-to-hyperalgesia-through-the-spinal-inflammatory-mediator-cgrp-in-mice
#7
Ya-Tin Lin, Ho-Ling Liu, Yuan-Ji Day, Che-Chien Chang, Po-Hung Hsu, Jin-Chung Chen
Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia. BOLD signals from functional MRI showed that NPFFR2-Tg mice exhibited increased activation of pain-related brain regions after painful stimulation when compared to WT mice...
February 5, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28165287/cgrp-receptor-antagonist-activity-of-olcegepant-depends-on-the-signalling-pathway-measured
#8
Christopher S Walker, Ann C Raddant, Michael J Woolley, Andrew F Russo, Debbie L Hay
Background Calcitonin gene-related peptide (CGRP) is a neuropeptide that acts in the trigeminovascular system and is believed to play an important role in migraine. CGRP activates two receptors that are both present in the trigeminovascular system; the CGRP receptor and the amylin 1 (AMY1) receptor. CGRP receptor antagonists, including olcegepant (BIBN4096BS) and telcagepant (MK-0974), can treat migraine. This study aimed to determine the effectiveness of these antagonists at blocking CGRP receptor signalling in trigeminal ganglia (TG) neurons and transfected CGRP and AMY1 receptors in Cos7 cells, to better understand their mechanism of action...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28053042/induction-of-migraine-like-photophobic-behavior-in-mice-by-both-peripheral-and-central-cgrp-mechanisms
#9
Bianca N Mason, Eric A Kaiser, Adisa Kuburas, Maria-Cristina M Loomis, John A Latham, Leon F Garcia-Martinez, Andrew F Russo
The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. Although migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28025094/serotonergic-mechanisms-of-trigeminal-meningeal-nociception-implications-for-migraine-pain
#10
Erkan Kilinc, Cindy Guerrero-Toro, Andrey Zakharov, Carmela Vitale, Max Gubert-Olive, Ksenia Koroleva, Arina Timonina, Liliana L Luz, Irina Shelukhina, Raisa Giniatullina, Fatma Tore, Boris V Safronov, Rashid Giniatullin
Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28001346/analgesic-microneedle-patch-for-neuropathic-pain-therapy
#11
Xi Xie, Conrado Pascual, Christopher Lieu, Seajin Oh, Ji Wang, Bende Zou, Julian Xie, Zhaohui Li, James Xie, David C Yeomans, Mei X Wu, Xinmin Simon Xie
Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain...
January 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/27940880/cgrp-in-human-models-of-primary-headaches
#12
Håkan Ashina, Henrik Winther Schytz, Messoud Ashina
OBJECTIVE: To review the role of CGRP in human models of primary headaches and to discuss methodological aspects and future directions. DISCUSSION: Provocation experiments demonstrated a heterogeneous CGRP migraine response in migraine patients. Conflicting CGRP plasma results in the provocation experiments are likely due to assay variation; therefore, proper validation and standardization of an assay is needed. To what extent CGRP is involved in tension-type headache and cluster headache is unknown...
December 9, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#13
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27909097/induction-of-migraine-like-photophobic-behavior-in-mice-by-both-peripheral-and-central-cgrp-mechanisms
#14
Bianca N Mason, Eric A Kaiser, Adisa Kuburas, Maria-Cristina M Loomis, John A Latham, Leon F Garcia-Martinez, Andrew F Russo
The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. While migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the central nervous system, we used CGRP-induced light aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal, IP) injection of CGRP resulted in light aversive behavior in wild-type CD1 mice similar to aversion previously seen following central (intracerebroventricular, ICV) injection...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27884929/pro-nociceptive-migraine-mediator-cgrp-provides-neuroprotection-of-sensory-cortical-and-cerebellar-neurons-via-multi-kinase-signaling
#15
Polina A Abushik, Geneviève Bart, Paula Korhonen, Hanna Leinonen, Raisa Giniatullina, Dmitry A Sibarov, Anna-Liisa Levonen, Tarja Malm, Sergei M Antonov, Rashid Giniatullin
BACKGROUND: Blocking the pro-nociceptive action of CGRP is one of the most promising approaches for migraine prophylaxis. The aim of this study was to explore a role for CGRP as a neuroprotective agent for central and peripheral neurons. METHODS: The viability of isolated rat trigeminal, cortical and cerebellar neurons was tested by fluorescence vital assay. Engagement of Nrf2 target genes was analyzed by qPCR. The neuroprotective efficacy of CGRP in vivo was tested in mice using a permanent cerebral ischemia model...
November 24, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27865545/anti-cgrp-antibodies-block-cgrp-induced-diarrhea-in-mice
#16
Eric A Kaiser, Brandon J Rea, Adisa Kuburas, Brian R Kovacevich, Leon F Garcia-Martinez, Ana Recober, Andrew F Russo
The multifunctional neuropeptide calcitonin gene-related peptide (CGRP) and its receptor are expressed throughout the gastrointestinal tract. Previous studies have shown that CGRP has roles in intestinal motility, water secretion, and inflammation. Furthermore, animal studies have demonstrated CGRP involvement in diarrhea secondary to C. difficile and food allergies. Diarrhea thus provides a convenient bioassay of CGRP activity in the GI system. In this proof of principle study, we report that prophylactic administration of an anti-CGRP antibody is able to block CGRP-induced diarrhea in mice...
November 14, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27834685/antagonism-of-cannabinoid-receptor-1-attenuates-the-anti-inflammatory-effects-of-electroacupuncture-in-a-rodent-model-of-migraine
#17
Hui Zhang, Shengdong He, Youping Hu, Hui Zheng
BACKGROUND: The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials. Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor. OBJECTIVE: To investigate whether CB1 receptors mediate the anti-inflammatory effects of EA on migraine attacks. METHODS: A migraine model was produced in Sprague-Dawley rats by unilateral electrical stimulation of the trigeminal ganglion (TGES)...
December 2016: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/27791151/targeting-cyp2j-to-reduce-paclitaxel-induced-peripheral-neuropathic-pain
#18
Marco Sisignano, Carlo Angioni, Chul-Kyu Park, Sascha Meyer Dos Santos, Holger Jordan, Maria Kuzikov, Di Liu, Sebastian Zinn, Stephan W Hohman, Yannick Schreiber, Béla Zimmer, Mike Schmidt, Ruirui Lu, Jing Suo, Dong-Dong Zhang, Stephan M G Schäfer, Martine Hofmann, Ajay S Yekkirala, Natasja de Bruin, Michael J Parnham, Clifford J Woolf, Ru-Rong Ji, Klaus Scholich, Gerd Geisslinger
Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe dose- and therapy-limiting side effect of widely used cytostatics that is particularly difficult to treat. Here, we report increased expression of the cytochrome-P450-epoxygenase CYP2J6 and increased concentrations of its linoleic acid metabolite 9,10-EpOME (9,10-epoxy-12Z-octadecenoic acid) in dorsal root ganglia (DRGs) of paclitaxel-treated mice as a model of CIPNP. The lipid sensitizes TRPV1 ion channels in primary sensory neurons and causes increased frequency of spontaneous excitatory postsynaptic currents in spinal cord nociceptive neurons, increased CGRP release from sciatic nerves and DRGs, and a reduction in mechanical and thermal pain hypersensitivity...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27786243/new-strategies-for-the-treatment-and-prevention-of-primary-headache-disorders
#19
REVIEW
Nathaniel M Schuster, Alan M Rapoport
The primary headache disorders, which include migraine, cluster headache and tension-type headache, are among the most common diseases and leading causes of disability worldwide. The available treatment options for primary headache disorders have unsatisfactory rates of efficacy, tolerability and patient adherence. In this Review, we discuss promising new approaches for the prevention of primary headache disorders, such as monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor, and small-molecule CGRP receptor antagonists...
October 27, 2016: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/27756950/role-of-fosaprepitant-a-neurokinin-type-1-receptor-antagonist-in-morphine-induced-antinociception-in-rats
#20
Pranav Prasoon, Shivani Gupta, Rahul Kumar, Mayank Gautam, Saroj Kaler, Subrata Basu Ray
OBJECTIVES: Opioids such as morphine form the cornerstone in the treatment of moderate to severe pain. However, opioids also produce serious side effects such as tolerance. Fosaprepitant is a substance P (SP) receptor antagonist, which is used for treating chemotherapy-induced nausea and vomiting. SP is an important neuropeptide mediating transmission of pain at the spinal level. Thus, it was hypothesized that combining morphine with fosaprepitant would increase the antinociceptive effect of morphine...
July 2016: Indian Journal of Pharmacology
keyword
keyword
66176
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"