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Sumatriptan mechanisms

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...
September 28, 2016: Brain Injury: [BI]
Carlos M Villalón, Antoinette Maassen VanDenBrink
Migraine is a highly prevalent neurovascular disorder. 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. More direct evidence comes from some drugs that influence 5-HT release and/or interact (as agonists or antagonists) with 5-HT receptors to treat this disorder...
July 28, 2016: Mini Reviews in Medicinal Chemistry
Fereshteh Farajdokht, Shirin Babri, Pouran Karimi, Gisou Mohaddes
Systemic administration of nitroglycerin (NTG) consistently provokes spontaneous-like migraine attacks in migraine sufferers, and in rat it induces hyperalgesia and allodynia. In the present study we modeled migraine headache by intraperitoneal (i.p.) injection of a single dose of NTG, which produced widespread thermal allodynia and mechanical hyperalgesia, photophobia, and increased anxiety-like behaviors and serum concentration of cortisol. Results suggest that the effects of NTG can be largely reversed by administration of ghrelin, which mimics the effects of sumatriptan used as relevant positive therapeutic control in this study...
September 6, 2016: Neuroscience Letters
L Venkatraghavan, L Li, T Bailey, P H Manninen, M Tymianski
BACKGROUND: Microvascular decompression (MVD) is a surgical treatment for cranial nerve disorders via a small craniotomy. The postoperative pain of this procedure can be classified as surgical site somatic pain and postcraniotomy headache similar in nature to a migraine, including its association with photophobia, nausea, and vomiting. This headache can be difficult to treat and can impact on postoperative recovery. Sumatriptan is used to treat migraine-like headaches in various settings...
July 2016: British Journal of Anaesthesia
Vahid Nikoui, Mehrak Javadi-Paydar, Mahtab Salehi, Selda Behestani, Ahmad-Reza Dehpour
Lithium is a drug used for the treatment of bipolar disorder. It has several mechanisms of action, and recently it is shown that lithium can antagonize the 5-HT1B/1D serotonin receptors. Sumatriptan is a 5-HT1B/1D receptor agonist used for the treatment of cluster headaches and migraine which might cause memory impairment as a potential side effect. In this study, effects of lithium on sumatriptan-induced memory impairment have been determined in a two-trial recognition Y-maze and passive avoidance tests. Male mice weighing 25-30 g were divided into several groups randomly...
April 2016: Acta Medica Iranica
Caroline Machado Kopruszinski, Jennifer Yanhua Xie, Nathan Mackenzie Eyde, Bethany Remeniuk, Sarah Walter, Jennifer Stratton, Marcelo Bigal, Juliana Geremias Chichorro, David Dodick, Frank Porreca
OBJECTIVE: The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. METHODS: Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP antibody...
May 19, 2016: Cephalalgia: An International Journal of Headache
Isabella Telò, Elena Tratta, Barbara Guasconi, Sara Nicoli, Silvia Pescina, Paolo Govoni, Patrizia Santi, Cristina Padula
Buccal administration of sumatriptan succinate might be an interesting alternative to the present administration routes, due to its non-invasiveness and rapid onset of action, but because of its low permeability, a permeation enhancement strategy is required. The aim of this work was then to study, in-vitro, buccal iontophoresis of sumatriptan succinate. Permeation experiments were performed in-vitro across pig esophageal epithelium, a recently proposed model of human buccal mucosa, using vertical diffusion cells...
June 15, 2016: International Journal of Pharmaceutics
Simon Law, Sheena Derry, R Andrew Moore
BACKGROUND: This is an updated version of the original Cochrane review published in October 2013 on 'Sumatriptan plus naproxen for acute migraine attacks in adults'.Migraine is a common disabling condition and a burden for the individual, health services, and society. It affects two to three times more women than men, and is most common in the age range 30 to 50 years. Effective abortive treatments include the triptan and non-steroidal anti-inflammatory classes of drugs. These drugs have different mechanisms of action and combining them may provide better relief...
2016: Cochrane Database of Systematic Reviews
Dioneia Araldi, Luiz F Ferrari, Jon D Levine
We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein-coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act at 5-HT1B/D Gi-GPCRs, have been implicated in pain chronification. We determined whether sumatriptan, a prototypical 5-HT1B/D agonist, produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2 (PGE2) induces prolonged mechanical hyperalgesia...
August 2016: Pain
Dongyue Huang, Lynn Ren, Chang-Shen Qiu, Ping Liu, Jonathan Peterson, Yuchio Yanagawa, Yu-Qing Cao
Migraine and other primary headache disorders affect a large population and cause debilitating pain. Establishing animal models that display behavioral correlates of long-lasting and ongoing headache, the most common and disabling symptom of migraine, is vital for the elucidation of disease mechanisms and identification of drug targets. We have developed a mouse model of headache, using dural application of capsaicin along with a mixture of inflammatory mediators (IScap) to simulate the induction of a headache episode...
August 2016: Pain
Mohammad Sohail Asghar, Lino Becerra, Henrik B W Larsson, David Borsook, Messoud Ashina
BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded blood-oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve...
2016: PloS One
Annelien De Pue, Bart Lutin, Koen Paemeleire
BACKGROUND: Cluster headache is classified as a primary headache by definition not caused by an underlying pathology. However, symptomatic cases of otherwise typical cluster headache have been reported. CASE PRESENTATION: A 47-year-old male suffered from primary chronic cluster headache (CCH, ICHD-3 beta criteria fulfilled) since the age of 35 years. A magnetic resonance imaging (MRI) study of the brain in 2006 came back normal. He tried several prophylactic treatments but was never longer than 1 month without attacks...
2016: Journal of Headache and Pain
L F Ferrari, J D Levine, P G Green
Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN's very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay...
March 11, 2016: Neuroscience
Alycia F Tipton, Igal Tarash, Brenna McGuire, Andrew Charles, Amynah A Pradhan
BACKGROUND: The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models. We have recently developed a new mouse model of chronic migraine using chronic intermittent nitroglycerin, a known human migraine trigger. The objective of this study was to validate this model by testing known and potential migraine-preventive treatments. METHODS: Migraine therapies were administered to male and female mice for 11 days...
December 17, 2015: Cephalalgia: An International Journal of Headache
Zdravko Lacković, Boris Filipović, Ivica Matak, Zsuzsanna Helyes
BACKGROUND AND PURPOSE: Although botulinum toxin type A (BoNT/A) is approved for chronic migraine treatment, its mechanism of action is still unknown. Dural neurogenic inflammation (DNI) commonly used to investigate migraine pathophysiology can be evoked by trigeminal pain. Here, we investigated the reactivity of cranial dura to trigeminal pain and the mechanism of BoNT/A action on DNI. EXPERIMENTAL APPROACH: Because temporomandibular disorders are highly comorbid with migraine, we employed a rat model of inflammation induced by complete Freund's adjuvant, followed by treatment with BoNT/A injections or sumatriptan p...
January 2016: British Journal of Pharmacology
Roberta Carbonara, Alessia Carocci, Julien Roussel, Giuseppe Crescenzo, Canio Buonavoglia, Carlo Franchini, Giovanni Lentini, Diana Conte Camerino, Jean-François Desaphy
Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. In a previous study, we evaluated the analgesic activity of sumatriptan, an agonist of serotonin 5HT1B/D receptors, and some new chiral bioisosteres, using the hot plate test in the mouse...
2015: Frontiers in Pharmacology
Priyoneel Basu, Naomi Ie, Adrienne L Wensel, Joelle D Baskerville, Victoria M Smith, Michael C Antle
Daily exposure to light synchronizes the circadian clock, located in the suprachiasmatic nucleus (SCN), to external day/night cycles. These responses to light can be modified by serotonergic drugs, such as serotonin 5HT1B receptor agonists. Triptans are specific 5HT1B agonists prescribed to treat migraines. Here, we examined the effects of two triptans (zolmitriptan and sumatriptan) on photic phase resetting in Syrian hamsters. Pre-treatment with intra-SCN sumatriptan significantly attenuates, and at higher doses completely blocks, phase advances to light during the late night...
October 2015: European Journal of Neuroscience
Inga L Kröger, Arne May
OBJECTIVE: The 5-HT1B/D agonists (triptans) are specific headache medications that have no effect on pain as such. Although they are routinely used in the treatment of acute migraine attacks, the underlying mechanisms of action are still a matter of debate. METHODS: Forty-three healthy participants underwent fMRI while receiving trigemino-nociceptive stimulation and control stimuli in a standardized fMRI paradigm. Using a crossover, double-blind, placebo-controlled design, 21 participants (10 women, mean age 26...
May 26, 2015: Neurology
Carolina C Burgos-Vega, David Dong-Uk Ahn, Christina Bischoff, Weiya Wang, Dan Horne, Judy Wang, Narender Gavva, Gregory Dussor
BACKGROUND: Migraine headache is a neurological disorder affecting millions worldwide. However, little is known about the mechanisms contributing to migraine. Recent genome-wide association studies have found single nucleotide polymorphisms in the gene encoding transient receptor potential channel M8. Transient receptor potential channel M8 is generally known as a cold receptor but it has been implicated in pain signaling and may play a role in migraine pain. METHODS: In order to investigate whether transient receptor potential channel M8 may contribute to the pain of migraine, the transient receptor potential channel M8 activator icilin was applied to the dura mater using a rat behavioral model of headache...
February 2016: Cephalalgia: An International Journal of Headache
Vijeta Bobade, Subhash L Bodhankar, Urmila Aswar, Mohan Vishwaraman, Prasad Thakurdesai
The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia...
April 2015: Chinese Journal of Natural Medicines
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