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https://www.readbyqxmd.com/read/28880380/faster-improvement-in-migraine-pain-intensity-and-migraine-related-disability-at-early-time-points-with-avp-825-sumatriptan-nasal-powder-delivery-system-versus-oral-sumatriptan-a-comparative-randomized-clinical-trial-across-multiple-attacks-from-the-compass
#1
Richard B Lipton, James S McGinley, Kenneth J Shulman, R J Wirth, Dawn C Buse
BACKGROUND: Fast relief of migraine pain, associated symptoms, and migraine-related disability are priorities in the acute treatment of migraine. Efforts to improve the pharmacokinetic profiles of acute migraine treatments with the aim of providing faster relief include the development of non-oral routes of administration. AVP-825 (ONZETRA(®) Xsail(®) ) is a delivery system containing 22 mg sumatriptan powder that uses a patient's own breath to deliver medication intranasally, targeting the upper posterior nasal cavity beyond the narrow nasal valve, an area lined with vascular mucosa conducive to rapid drug absorption into the systemic circulation...
September 7, 2017: Headache
https://www.readbyqxmd.com/read/28815720/pharmacological-evidence-of-involvement-of-nitric-oxide-pathway-in-anti-pruritic-effects-of-sumatriptan-in-chloroquine-induced-scratching-in-mice
#2
Nazgol-Sadat Haddadi, Sattar Ostadhadi, Saeed Shakiba, Khashayar Afshari, Nastaran Rahimi, Arash Foroutan, Ahmad-Reza Dehpour
Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatriptan, a 5-hydroxytryptamine 1b/1d receptors (5-HTR1b/1d) agonist, is involved in pain and used to treat migraine and cluster headaches. According to previous studies, sumatriptan inhibits NOS activity...
August 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28792272/trigeminovascular-calcitonin-gene-related-peptide-function-in-cacna1a-r192q-mutated-knock-in-mice
#3
Kayi Y Chan, Alejandro Labastida-Ramírez, Martha B Ramírez-Rosas, Sieneke Labruijere, Ingrid M Garrelds, Alexander Hj Danser, Arn Mjm van den Maagdenberg, Antoinette MaassenVanDenBrink
Familial hemiplegic migraine type 1 (FHM1) is a rare migraine subtype. Whereas transgenic knock-in mice with the human pathogenic FHM1 R192Q missense mutation in the Cacna1a gene reveal overall neuronal hyperexcitability, the effects on the trigeminovascular system and calcitonin gene-related peptide (CGRP) receptor are largely unknown. This gains relevance as blockade of CGRP and its receptor are therapeutic targets under development. Hence, we set out to test these effects in FHM1 mice. We characterized the trigeminovascular system of wild-type and FHM1 mice through: (i) in vivo capsaicin- and CGRP-induced dural vasodilation in a closed-cranial window; (ii) ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion and trigeminal nucleus caudalis; and (iii) peripheral vascular function in vitro ...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28782480/recent-progress-in-biological-activities-of-indole-and-indole-alkaloids
#4
O M Singh, Thokchom Prasanta Singh
The indole scaffold is a prominent and privileged structural motif found in numerous natural products and in a wide range of bioactive heterocycles. Starting from the simple structural framework of serotonin, the well known neurotransmitter to complex alkaloids which are used clinically as anticancer agent, mitomycin C, and the antihypertensive alkaloid reserpine, the indole moiety is considered as the active principle. Thus over the past decade, a large number of indole-containing compounds have revealed remarkable pharmacological activity and their utility as therapeutic agents have attracted considerable attention from chemists...
August 7, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28758416/pregnancy-outcome-after-anti-migraine-triptan-use-a-prospective-observational-cohort-study
#5
Kevin Spielmann, Angela Kayser, Evelin Beck, Reinhard Meister, Christof Schaefer
Objective The objective of our study is to assess the impact of triptan exposure on pregnancy outcome. Methods We performed a prospective observational cohort study with 432 pregnant women exposed to triptans and enrolled by the German Embryotox system. Pregnancy outcomes were compared with a migraine and a non-migraine comparison cohort. Primary objectives were major birth defects and spontaneous abortion; secondary endpoints were preterm delivery, birth weight, pregnancy complications and the rate of electively terminated pregnancies...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28751192/evidence-of-an-inverse-correlation-between-serotonergic-activity-and-spreading-depression-propagation-in-the-rat-cortex
#6
Rubem Carlos Araújo Guedes, Maria das Graças Rodrigues de Araújo, Taciana Cristovam Verçosa, Francisca Martins Bion, Andrea Lima de Sá, Antônio Pereira, Ricardo Abadie-Guedes
Various neurological and psychiatric diseases lead to alterations in cortical serotonergic activity as one of their underlying processes. However, the electrophysiological implication of changes in serotonergic activity remains a matter of investigation. In this study, we investigated whether brain serotonergic activity influences the excitability-related phenomenon known as cortical spreading depression (CSD). CSD parameters (propagation velocity, and amplitude and duration of the DC-shift) was evaluated in rats that received two treatments that increased cortical serotonergic activity, electrical stimulation of the raphe nuclei and subcutaneous injection of a selective serotonin reuptake inhibitor, sumatriptan...
October 1, 2017: Brain Research
https://www.readbyqxmd.com/read/28741429/rapid-systemic-delivery-of-zolmitriptan-using-an-adhesive-dermally-applied-microarray
#7
Donald J Kellerman, Mahmoud Ameri, Stewart J Tepper
Adhesive Dermally-Applied Microarray (ADAM) is a device for intracutaneous drug administration consisting of a 3 cm(2) disposable array of drug-coated titanium microprojections on an adhesive backing. It is applied using a low cost, reusable, handheld applicator. Microprojections penetrate the stratum corneum, delivering drug proximal to capillaries with limited likelihood of pain. The pharmacokinetics of zolmitriptan delivery using ADAM was evaluated in 20 healthy volunteers. Median tmax was <20 min, comparable to subcutaneous sumatriptan...
July 25, 2017: Pain Management
https://www.readbyqxmd.com/read/28717987/interventions-for-refractory-trigeminal-neuralgia-a-bayesian-mixed-treatment-comparison-network-meta-analysis-of-randomized-controlled-clinical-trials
#8
Kannan Sridharan, Gowri Sivaramakrishnan
INTRODUCTION: Patients with trigeminal neuralgia (TN) are often refractory to recommended first-line agents. Due to the absence of a systematic review, we undertook a network meta-analysis to assess various interventions that can be used to manage refractory TN. METHODS: Electronic databases were searched using appropriate strategies to identify randomized controlled clinical trials in patients with refractory TN, evaluating the proportion of patients with a minimum of 50% reduction in pain or a minimum of 2 cm reduction in score in an appropriate pain scale or complete pain relief by subjective pain scales...
July 17, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28691382/variation-in-prescription-drug-coverage-for-triptans-analysis-of-insurance-formularies
#9
Mia T Minen, Kate Lindberg, Aisha Langford, Elizabeth Loder
OBJECTIVES: To analyze triptan coverage by insurers to examine (1) possible disparities in coverage for different formulations (oral, intranasal, etc) and (2) quantity limits and stepped care requirements to obtain triptans. BACKGROUND: Triptans are FDA approved migraine abortive medications. Patients frequently state that they have difficulty accessing triptans prescribed to them. METHODS: We searched the 2015 drug formularies of commercial and government health insurers providing coverage in NY State...
July 9, 2017: Headache
https://www.readbyqxmd.com/read/28678396/animal-model-of-chronic-migraine-associated-pain
#10
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/28618340/fast-and-efficient-zirconia-based-reversed-phase-chromatography-for-selective-determination-of-triptans-in-rat-plasma
#11
Sameh Ahmed, Noha N Atia
Selective and fast chromatographic method was essential for the determination of triptans, selective serotonin receptor (5-HT1) agonists, in biological specimens. However, selective chromatographic separation of these highly basic drugs is a challenging problem on silica-based stationary phases. Zirconia-based stationary phases have been introduced as an efficient alternative for silica-based columns offering unique stability, selectivity, and retention ability for various classes of drugs. Herein, a new selective, fast and reproducible high performance liquid chromatographic method (HPLC) was developed and validated for the determination of four triptans in plasma samples namely; Sumatriptan (SMT), Zolmitriptan (ZLT), Eletriptan (ELT) and Rizatriptan (RZT)...
September 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28605258/avp-825-a-novel-intranasal-delivery-system-for-low-dose-sumatriptan-powder-in-the-treatment-of-acute-migraine
#12
REVIEW
Stephen Silberstein
Migraine is a common, disabling disorder, and many patients remain dissatisfied with existing treatments. AVP-825 (ONZETRA® Xsail®) is a Breath Powered® exhalation delivery system for low-dose sumatriptan nasal powder (22 mg) that has been recently approved for use in the treatment of acute migraine with or without aura in adults. AVP-825 takes advantage of unique features of nasal anatomy and physiology to avoid limitations typically seen with other types of intranasal medication delivery. Areas covered: This review provides a summary of the pharmacology, clinical efficacy and tolerability of AVP-825 in clinical studies to date and also provides an overview of the unique aspects of the delivery system...
August 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28599085/exploring-the-putative-role-of-trpv1-dependent-cgrp-release-in-remote-hind-preconditioning-induced-cardioprotection
#13
Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) is a phenomenon whereby transient non-lethal ischemia and reperfusion episodes confer protection against prolonged ischemia-reperfusion-induced injury. However, the underlying intracellular signaling has not been extensively explored. The present study aims to inspect the putative involvement of TRPV1 -dependent CGRP release in mediating remote hind limb preconditioning-induced cardioprotection. In the present study, remote hind limb preconditioning stimulus was delivered (4 consecutive episodes of 5 minutes of ischemia-reperfusion) using a blood pressure cuff tied at the inguinal level of the rat...
June 9, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28597922/pharmacokinetic-characterization-and-dose-selection-of-a-novel-sumatriptan-nasal-spray-formulation-dfn-02
#14
Arindam Pal, Anirudh Gautam, Sagar Munjal
This 3-way, single-dose, randomized crossover study evaluated the pharmacokinetics (PK) and dose proportionality of 5-, 10-, and 15-mg doses of intranasal sumatriptan (DFN-02) coformulated with a permeation enhancer (DDM) in 18 healthy adults. The objective was to determine which DFN-02 dose approximates the PK of a 6-mg dose of sumatriptan delivered via subcutaneous injection in the deltoid muscle of the arm. Sumatriptan plasma concentrations peaked with DFN-02 between 10 and 15 minutes postdose, declining thereafter, with a t1/2 of about 2...
June 9, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28579821/opioid-analgesics-related-pharmacokinetic-drug-interactions-from-the-perspectives-of-evidence-based-on-randomized-controlled-trials-and-clinical-risk-management
#15
REVIEW
Xiu-Qin Feng, Ling-Ling Zhu, Quan Zhou
BACKGROUND: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs). METHOD: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart...
2017: Journal of Pain Research
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
#16
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
#17
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/28527055/cluster-headache-present-and-future-therapy
#18
Massimo Leone, Alessandro Giustiniani, Alberto Proietti Cecchini
Cluster headache is characterized by severe, unilateral headache attacks of orbital, supraorbital or temporal pain lasting 15-180 min accompanied by ipsilateral lacrimation, rhinorrhea and other cranial autonomic manifestations. Cluster headache attacks need fast-acting abortive agents because the pain peaks very quickly; sumatriptan injection is the gold standard acute treatment. First-line preventative drugs include verapamil and carbolithium. Other drugs demonstrated effective in open trials include topiramate, valproic acid, gabapentin and others...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28527054/understanding-migraine-as-a-cycling-brain-syndrome-reviewing-the-evidence-from-functional-imaging
#19
Arne May
Due to the clinical picture and also based on early imaging data (Weiller et al. Nat Med 1:658-660, 1995), the brainstem and midbrain structures have been intensely discussed as possible driving or generating structures in migraine. The fact that the brainstem activation persisted after treatment makes it unlikely that this activation was only due to increased activity of the endogenous anti-nociceptive system. It was consequently (and somewhat simplifying) coined the "migraine generator". Since then several studies have focussed on this region when investigating episodic, but also chronic migraine...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28497569/early-onset-of-efficacy-and-consistency-of-response-across-multiple-migraine-attacks-from-the-randomized-compass-study-avp-825-breath-powered-%C3%A2-exhalation-delivery-system-sumatriptan-nasal-powder-vs-oral-sumatriptan
#20
Stephen Silberstein, Paul K Winner, Peter J McAllister, Stewart J Tepper, Rashmi Halker, Ramy A Mahmoud, Joao Siffert
OBJECTIVE: To further characterize the clinical utility of AVP-825 based on additional prespecified outcomes and post hoc analyses of COMPASS, a Phase 3 comparative efficacy trial of AVP-825 vs 100 mg oral sumatriptan (NCT01667679). AVP-825 was approved in January 2016 by the US Food and Drug Administration under the name ONZETRA(®) Xsail(®) (sumatriptan nasal powder) for the acute treatment of migraine with or without aura in adults. BACKGROUND: AVP-825 is a delivery system that uses a patient's own breath to deliver low-dose sumatriptan powder to the upper posterior regions of the nasal cavity beyond the narrow nasal valve, areas lined with vascular mucosa conducive to rapid drug absorption into the systemic circulation...
June 2017: Headache
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