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Sumatriptan mechanisms

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https://www.readbyqxmd.com/read/29382888/a-unique-inbred-rat-strain-with-sustained-cephalic-hypersensitivity-as-a-model-of-chronic-migraine-like-pain
#1
Gordon Munro, Steffen Petersen, Inger Jansen-Olesen, Jes Olesen
Animal models of migraine-like pain enabling ongoing study of behaviour typically involve the systemic administration of chemical vasodilators or dural administration of inflammatory algogens. However, neither method mediates prolonged effects on behavior indicative of enduring pathophysiological changes occurring within dural or trigeminal pain circuits. We generated successive generations of a unique inbred rat strain, spontaneous trigeminal allodynia (STA) rats, previously reported to exhibit an episodic migraine-like behavioural phenotype...
January 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29371973/17-%C3%AE-estradiol-induces-spreading-depression-and-pain-behavior-in-alert-female-rats
#2
Alexander J Sandweiss, Karissa E Cottier, Mary I McIntosh, Gregory Dussor, Thomas P Davis, Todd W Vanderah, Tally M Largent-Milnes
Aims: Test the putative contribution of 17-β-estradiol in the development of spreading depression (SD) events and head pain in awake, non-restrained rats. Main Methods: Female, Sprague-Dawley rats were intact or underwent ovariectomy followed one week later by surgery to place electrodes onto the dura to detect epidural electroencephalographic activity (dEEG). dEEG activity was recorded two days later for 12 hours after systemic administration of 17-β-estradiol (180 μg/kg, i...
December 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/29200178/induction-of-chronic-migraine-phenotypes-in-a-rat-model-after-environmental-irritant-exposure
#3
Phillip Edward Kunkler, LuJuan Zhang, Philip Lee Johnson, Gerry Stephen Oxford, Joyce Harts Hurley
Air pollution is linked to increased emergency room visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well-understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for 4 days prior to meningeal blood flow measurements, periorbital cutaneous sensory testing or other behavioral testing...
December 1, 2017: Pain
https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#4
Manel Ben Aissa, Alycia F Tipton, Zachariah Bertels, Ronak Gandhi, Laura S Moye, Madeline Novack, Brian M Bennett, Yueting Wang, Vladislav Litosh, Sue H Lee, Irina N Gaisina, Gregory Rj Thatcher, Amynah A Pradhan
Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28952321/cilostazol-induces-c-fos-expression-in-the-trigeminal-nucleus-caudalis-and-behavioural-changes-suggestive-of-headache-with-the-migraine-like-feature-photophobia-in-female-rats
#5
S L Christensen, Steffen Petersen, Dorte B Sørensen, Jes Olesen, Inger Jansen-Olesen
Introduction Research in development of new migraine therapeutics is hindered by the lack of suitable, predictive animal models. Cilostazol provokes headache in healthy humans and migraineurs by increasing intracellular cAMP levels. We aimed to investigate whether cilostazol could provoke headache-like behaviours and c-fos expression in rats. In order to evaluate the predictive validity of the model, we examined the response to the migraine specific drug sumatriptan. Methods The effect of cilostazol (125 mg/kg p...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28678396/animal-model-of-chronic-migraine-associated-pain
#6
Laura S Moye, Amynah A A Pradhan
Migraine is a debilitating condition that affects hundreds of millions of people worldwide. A subset of these patients experience chronic migraine, resulting in long-term disability and a severely lowered quality of life. The development of novel migraine therapies has been slow, partially due to the small number of predictive animal models. We have recently developed a novel model of chronic migraine-associated pain, using the known human migraine trigger, nitroglycerin. Injection of nitroglycerin evokes an acute mechanical hyperalgesia, which is sensitive to the acute migraine therapy sumatriptan...
July 5, 2017: Current Protocols in Neuroscience
https://www.readbyqxmd.com/read/28565942/recurrent-administration-of-the-nitric-oxide-donor-isosorbide-dinitrate-induces-a-persistent-cephalic-cutaneous-hypersensitivity-a-model-for-migraine-progression
#7
Radhouane Dallel, Amélie Descheemaeker, Philippe Luccarini
Background A subgroup of migraineurs experience an increase in attack frequency leading to chronic migraine. Methods We assessed in rats the roles of dose and repeat administration of systemic isosorbide dinitrate (ISDN), a nitric oxide donor, on the occurrence and development of cephalic/face and extracephalic/hindpaw mechanical allodynia as a surrogate of migraine pain, and the effect of acute systemic sumatriptan and olcegepant and chronic systemic propranolol on these behavioral changes. Results A single high (H-ISDN) but not low (L-ISDN) dose of ISDN induces a reversible cephalic and extracephalic mechanical allodynia...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28562545/sumatriptan-induced-angle-closure-glaucoma-a-case-report
#8
Cherng-Ru Hsu, Yi-Hao Chen, Ming-Cheng Tai, Da-Wen Lu
RATIONALE: Drug-induced bilateral angle-closure glaucoma is a rare event and should be treated correctly and promptly to prevent visual loss. PATIENT CONCERNS: We report a rare case of sumatriptan-induced bilateral angle-closure glaucoma in a young woman with migraine, and explore the possible mechanism. DIAGNOSES: We describe the clinical outcome of a patient with sumatriptan-induced bilateral angle-closure glaucoma. The patient presented with bilateral acute elevation of intraocular pressure (IOP) and myopic shift...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28283434/insights-into-the-molecular-mechanism-of-triptan-transport-by-p-glycoprotein
#9
Laura A Wilt, Diana Nguyen, Arthur G Roberts
The P-glycoprotein (Pgp) transporter reduces the penetration of a chemically diverse range of neurotherapeutics at the blood-brain barrier, but the molecular features of drugs and drug-Pgp interactions that drive transport remain to be clarified. In particular, the triptan neurotherapeutics, eletriptan (ETT) and sumatriptan (STT), were identified to have a >10-fold difference in transport rates despite being from the same drug class. Consistent with these transport differences, ETT activated Pgp-mediated ATP hydrolysis ∼2-fold, whereas STT slightly inhibited Pgp-mediated ATP hydrolysis by ∼10%...
March 7, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28194544/exploring-the-role-of-trpv-and-cgrp-in-adenosine-preconditioning-and-remote-hind-limb-preconditioning-induced-cardioprotection-in-rats
#10
Amritpal Singh, Puneet Kaur Randhawa, Anjana Bali, Nirmal Singh, Amteshwar Singh Jaggi
The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released...
February 14, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28103158/serotonin-receptor-targeted-therapy-for-migraine-treatment-an-overview-of-drugs-in-phase-i-and-ii-clinical-development
#11
REVIEW
Piero Barbanti, C Aurilia, G Egeo, L Fofi, R Palmirotta
Research has focused on serotonin (5-HT) 5-HT1D and 5-HT1F receptors to develop drugs acting through non-vasoconstrictive mechanisms for treating acute migraine and those targeting 5-HT2B and 5-HT7 receptors for preventing migraine. Areas covered: This paper reviews antimigraine drugs targeting 5-HT receptors in one phase I trial (sumatriptan iontophoretic transdermal system, TDS) and five phase II clinical trials (PNU-142633, LY334370, lasmiditan, NOX-188). Expert opinion: Data from our overview on investigational drugs in phase I and II clinical trials using the 5-HT1B/1D receptor agonist (sumatriptan TDS), 5-HT1D receptor agonist (PNU-142633), 5-HT1F receptor agonists (LY334370, lasmiditan) and a combined 5-HT1B/1D receptor agonist with nNOS inhibition (NOX-188) provided encouraging data for sumatriptan TDS and lasmiditan, disappointing results for PNU-142633, and promising findings for NOX-188...
March 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28101470/protective-roles-of-n-acetyl-cysteine-and-or-taurine-against-sumatriptan-induced-hepatotoxicity
#12
Javad Khalili Fard, Hossein Hamzeiy, Mohammadreza Sattari, Mohammad Ali Eghbal
Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28053042/induction-of-migraine-like-photophobic-behavior-in-mice-by-both-peripheral-and-central-cgrp-mechanisms
#13
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/28040566/marked-sexual-dimorphism-in-5-ht1-receptors-mediating-pronociceptive-effects-of-sumatriptan
#14
Dioneia Araldi, Luiz F Ferrari, Paul Green, Jon D Levine
Amongst the side effects of triptans, a substantial percentage of patients experience injection site pain and tenderness, the underlying mechanism of which is unknown. We found that the dose range from 10fg to 1000ng (intradermal) of sumatriptan induced a complex dose-dependent mechanical hyperalgesia in male rats, with distinct peaks, at 1pg and 10ng, but no hyperalgesia at 1ng. In contrast, in females, there was 1 broad peak. The highest dose (1000ng) did not produce hyperalgesia in either sex. We evaluated the receptors mediating sumatriptan hyperalgesia (1pg, 1 and 10ng)...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28025094/serotonergic-mechanisms-of-trigeminal-meningeal-nociception-implications-for-migraine-pain
#15
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...
April 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27909097/induction-of-migraine-like-photophobic-behavior-in-mice-by-both-peripheral-and-central-cgrp-mechanisms
#16
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/27899434/development-of-cgrp-dependent-pain-and-headache-related-behaviours-in-a-rat-model-of-concussion-implications-for-mechanisms-of-post-traumatic-headache
#17
Dara Bree, Dan Levy
BACKGROUND AND OBJECTIVE: Posttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a mild traumatic brain injury, or concussion. However, the mechanisms underlying PTH remain elusive, in part due to the lack of a clinically relevant animal model. Here, we characterized for the first time, headache and pain-related behaviours in a rat model of concussion evoked by a mild closed head injury (mCHI) - the major type of military and civilian related trauma associated with PTH - and tested responses to current and novel headache therapies...
November 29, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27866934/pharmacodynamic-action-and-mechanism-of-du-liang-soft-capsule-a-traditional-chinese-medicine-capsule-on-treating-nitroglycerin-induced-migraine
#18
Min Hou, Qing Tang, Qiang Xue, Xiaona Zhang, Yang Liu, Sheng Yang, Liechun Chen, Xiaoyu Xu
ETHNOPHARMACOLOGICAL RELEVANCE: Du Liang soft capsule (DL) is a traditional Chinese medicine for treating migraines; it is made from two Chinese herbs, including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root. AIM OF THE STUDY: In the present study, we aimed to elucidate the pharmacodynamic action of DL and its mechanism in an animal model of migraines induced by glyceryl trinitrate (GTN). MATERIALS AND METHODS: Sixty rats were randomly divided into six groups, including a normal control group, model control group, positive group (Sumatriptan 0...
January 4, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27680211/critical-neural-targets-for-the-level-of-human-consciousness-arousal-arrest-and-unconsciousness-after-sumatriptan-administration
#19
Jaakko W Långsjö, Kai Lehtimäki, Jyrki Ruohonen, Anne Sajanti, Satu Sandell, Hannu T Heikkilä, Antti Brander, Kari Saarinen, Lauri Herrala
BACKGROUND: Insufficient understanding of the mechanisms of consciousness can make unconsciousness a diagnostic challenge, directly effecting the treatment and the outcome of the patient. Consciousness is a product of brainstem arousal (wakefulness, the level of consciousness) and cortical information integration (awareness, the contents of consciousness). The thalamus serves as a critical hub in the arousal pathway. The nuclei within the internal medullary lamina, together with the associated thalamocortical connections, have been implicated as being especially important for human consciousness...
2016: Brain Injury: [BI]
https://www.readbyqxmd.com/read/27465216/the-role-of-5-hydroxytryptamine-in-the-pathophysiology-of-migraine-and-its-relevance-to-the-design-of-novel-treatments
#20
REVIEW
Carlos M Villalón, Antoinette Maassen VanDenBrink
BACKGROUND: Migraine is a highly prevalent neurovascular disorder. OBJECTIVE: Of the many factors that have been implicated over the years, 5-hydroxytryptamine (5-HT; serotonin) has long been involved in the pathophysiology of migraine. Certainly, some lines of evidence suggest: (i) a 5-HT depletion from blood platelets resulting in cranial extracerebral vasodilatation; and (ii) the effectiveness of an intravenous (i.v.) infusion of 5-HT to abort migraine in some patients...
2017: Mini Reviews in Medicinal Chemistry
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