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https://www.readbyqxmd.com/read/27852962/anatomy-and-immunochemical-characterization-of-the-non-arterial-peptidergic-diffuse-dural-innervation-of-the-rat-and-rhesus-monkey-implications-for-functional-regulation-and-treatment-in-migraine
#1
Frank L Rice, Jennifer Y Xie, Phillip J Albrecht, Emily Acker, Justin Bourgeois, Edita Navratilova, David W Dodick, Frank Porreca
OBJECTIVE: The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. METHODS: We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey...
November 16, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/26257653/inhibition-of-voltage-gated-sodium-channels-by-sumatriptan-bioisosteres
#2
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
https://www.readbyqxmd.com/read/25831967/modes-and-nodes-explain-the-mechanism-of-action-of-vortioxetine-a-multimodal-agent-mma-enhancing-serotonin-release-by-combining-serotonin-5ht-transporter-inhibition-with-actions-at-5ht-receptors-5ht1a-5ht1b-5ht1d-5ht7-receptors
#3
REVIEW
Stephen M Stahl
Vortioxetine is an antidepressant that targets multiple pharmacologic modes of action at sites--or nodes--where serotonergic neurons connect to various brain circuits. These multimodal pharmacologic actions of vortioxetine lead to enhanced release of various neurotransmitters, including serotonin, at various nodes within neuronal networks.
April 2015: CNS Spectrums
https://www.readbyqxmd.com/read/24118015/cannabidiol-reverses-the-mcpp-induced-increase-in-marble-burying-behavior
#4
Mirella Nardo, Plinio C Casarotto, Felipe V Gomes, Francisco S Guimarães
Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties. Recent results using the marble-burying test (MBT) suggest that CBD can also induce anticompulsive-like effects. Meta-chloro-phenyl-piperazine (mCPP) is a nonspecific serotonergic agonist (acting mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD patients and block the anticompulsive-like effect of serotonin reuptake inhibitors (SRIs) in animal models. The aim of this study was to investigate the interference of CBD on mCPP effects in repetitive burying...
October 2014: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/19548619/-plasma-membrane-depolarization-and-activation-of-receptors-for-endogenous-vasoconstrictors-as-possible-mechanisms-of-potentiation-of-vasoconstrictive-response-to-serotonin-in-traumatic-shock-in-rats
#5
L M Kozhevnikova, A G Davydova, P V Avdonin
The goal of this work was to study possible mechanisms underlying the potentiation of vasopressor response to serotonin observed in traumatic shock. Experiments with isolated aorta and mesenteric artery of the rat showed that vasoconstriction is caused by the activation of 5HT2A receptors. Agonists of 5HT1B, 5HT1D, 5HT2B, and 5HT4 receptors induced vasodilation. Agonists of 5HT1A receptors had a dual effect determined by interaction with alpha1-adrenergic receptors and 5HT1A receptors. Plasma membrane depolarization with 15 mM KCl increased the vasoconstrictive force in response to serotonin...
May 2009: Izvestiia Akademii Nauk. Seriia Biologicheskaia
https://www.readbyqxmd.com/read/19447184/measuring-the-risk-of-torsades-de-pointes-electrocardiographic-evaluation-of-pnu-142093-in-conscious-cynomolgus-non-human-primates-using-restraint-and-non-restraint-procedures
#6
COMPARATIVE STUDY
Alan S Bass, Laurie A Hanson, Terry A Jackson
OBJECTIVE: Drug-induced torsades de pointes (TdP) arrhythmia is a serious public health concern that has significantly slowed the advancement of promising new therapeutic agents to the marketplace. Modeling for the potential to produce TdP has relied in part on the surrogate biomarker QT interval prolongation, measured in vivo in animals and in the clinic in man. This study was a comparison of the effects of PNU-142093, a selective 5HT1D-serotonin receptor agonist, on QT interval prolongation under restraint and non-restraint conditions in conscious cynomolgus non-human primates...
July 2009: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/18568072/updated-overview-of-the-putative-role-of-the-serotoninergic-system-in-obsessive-compulsive-disorder
#7
Bruno Aouizerate, Dominique Guehl, Emmanuel Cuny, Alain Rougier, Pierre Burbaud, Jean Tignol, Bernard Bioulac
The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity...
September 2005: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/16120224/pharmacological-challenge-with-a-serotonin-1d-agonist-in-alcohol-dependence
#8
COMPARATIVE STUDY
Bavanisha Vythilingum, Charmaine J Hugo, J Stefan Maritz, Willie Pienaar, Dan J Stein
BACKGROUND: Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink...
2005: BMC Psychiatry
https://www.readbyqxmd.com/read/15891413/new-targets-in-the-acute-treatment-of-headache
#9
Peter J Goadsby
PURPOSE OF REVIEW: The aim of this article is to review recently identified targets for the acute treatment of primary headache disorders. RECENT FINDINGS: Calcitonin gene-related peptide (CGRP) receptor blockade has been shown to be an effective acute anti-migraine strategy and is a non-vasoconstrictor in terms of the mechanism of action. It is likely that direct blockade of CGRP release by inhibition of trigeminal nerves would be similarly effective in both migraine and cluster headache...
June 2005: Current Opinion in Neurology
https://www.readbyqxmd.com/read/15729745/association-analysis-of-monoamine-genes-with-measures-of-depression-and-anxiety-in-a-selected-community-sample-of-siblings
#10
M W Nash, K Sugden, P Huezo-Diaz, R Williamson, A Sterne, S Purcell, P C Sham, I W Craig
Evidence indicates the genetic susceptibility to depression and anxiety is both overlapping and dimensional. In the current study, a quantitative phenotype had been created from several depression and anxiety-related measures in order to index this common genetic susceptibility (G). This has been studied in 119 sibships comprising 312 individuals, selected for extreme scores on G, from a community-based sample of 34,371 individuals. In a pathway based candidate gene study, we examined five microsatellite markers located within or nearby to five serotonin system genes (5HT2C, 5HT1D, 5HT1B, TPH1, and MAOB)...
May 5, 2005: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/12172384/triptans-reduce-the-inflammatory-response-in-bacterial-meningitis
#11
Olaf Hoffmann, Nikolas Keilwerth, Margarethe Bastholm Bille, Uwe Reuter, Klemens Angstwurm, Ralf R Schumann, Ulrich Dirnagl, Joerg R Weber
Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans...
August 2002: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/11800504/sumatriptan-challenge-in-bipolar-patients-with-and-without-migraine-a-neuroendocrine-study-of-5-ht1d-receptor-function
#12
T Mahmood, T Silverstone, R Connor, P Herbison
An association between bipolar disorder and migraine has been lately recognized and an abnormality of central serotonergic function is suggested as the underlying neurophysiological disturbance. To examine the role of serotonin in bipolar disorder and migraine, we used the neuroendocrine challenge paradigm, and we chose sumatriptan, a 5HT1D agonist, as the pharmacological probe. We studied nine bipolar patients with migraine, nine bipolar patients without it, seven migraine patients, and nine matched normal controls...
January 2002: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/11371757/pharmacological-opportunities-and-pitfalls-in-the-therapy-of-migraine
#13
REVIEW
A May, P J Goadsby
The mild vasoconstrictor effects of modern antimigraine drugs, such as serotonin (5-HT; 5-hydroxytryptamine)1B/D agonists, have led to a search for nonvasoconstrictor approaches to therapy. Such approaches have included substance P (neurokinin I) antagonists, endothelin antagonists and highly specific 5HT1D agonists. All of these substances are effective in animal models and have no significant vasoconstrictive effects. However, all of them failed to demonstrate any antimigraine effects. Current clinical and experimental evidence therefore supports the view that isolated peripheral trigeminal nerve inhibition is insufficient to relieve acute migraine...
June 2001: Current Opinion in Neurology
https://www.readbyqxmd.com/read/10698088/sumatriptan-increases-the-proliferation-of-peripheral-blood-mononuclear-cells-from-hiv-infected-individuals-and-healthy-blood-donors-in-vitro
#14
P Afzelius, J O Nielsen
HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro...
January 2000: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/10631628/lack-of-pharmacokinetic-interaction-between-sumatriptan-and-naproxen
#15
RANDOMIZED CONTROLLED TRIAL
P Srinivasu, D Rambhau, B R Rao, Y M Rao
Sumatriptan is a 5HT1D agonist used in the treatment of migraine. Nonsteroidal anti-inflammatory drugs, beta-blockers, and calcium channel-blocking antagonists are used in the prophylaxis of migraine. Hence, there is a need to investigate the interaction of these prophylactic drugs with sumatriptan. The interaction of sumatriptan with propranolol, flunarizine, pizotifen, and butorphanol were reported earlier. Naproxen is shown to be effective in prophylactic treatment of migraine. In this study, the authors have investigated the circadian rhythm effect of naproxen on the pharmacokinetics of sumatriptan at 1000 and 2200 hours...
January 2000: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/10621951/single-photon-emission-computed-tomography-of-the-brain-with-tc-99m-hmpao-during-sumatriptan-challenge-in-obsessive-compulsive-disorder-investigating-the-functional-role-of-the-serotonin-auto-receptor
#16
RANDOMIZED CONTROLLED TRIAL
D J Stein, B Van Heerden, C J Wessels, J Van Kradenburg, J Warwick, H J Wasserman
1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbated by administration of certain serotonin agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar, 1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor plays an important role in this disorder (El Mansari et al, 1995). 2. In order to investigate the functional role of the serotonin auto-receptor in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo...
August 1999: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/10430113/hemodynamic-and-coronary-effects-of-intravenous-eletriptan-a-5ht1b-1d-receptor-agonist
#17
D F Muir, G P McCann, L Swan, A L Clark, W S Hillis
OBJECTIVE: To investigate the systemic, pulmonary, and coronary artery effects of eletriptan, a new 5HT1B/1D-agonist in patients undergoing cardiac catheterization. METHODS: Ten patients (two men and eight women) without significant obstructive coronary artery disease were administered 3.33 microg/kg/min intravenous eletriptan after they were given a placebo infusion of 0.9% saline solution. Serial measurements of right heart and systemic pressures were taken at 5-minute intervals during placebo infusion, eletriptan infusion, and a 30-minute postinfusion period...
July 1999: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/9928925/treatment-of-severe-drug-resistant-obsessive-compulsive-disorder-with-the-5ht1d-agonist-sumatriptan
#18
L Stern, J Zohar, R Cohen, Y Sasson
The serotonergic system has been implicated in both the aetiology and pharmacological treatment of obsessive compulsive disorder. In pharmacological challenge tests, mCPP, a 5-HT agonist, with an affinity for 5HT2C as well as 5HT1A and 5HT1D receptors, was associated with a transient exacerbation of obsessive compulsive symptoms. Chronic administration of mCPP was found to bring about some relief of these symptoms. Sumatriptan is an antimigraine agent, which interacts most potently with 5HT1D receptors. In the cases to be presented, we report the effects of chronic administration of Sumatriptan to three severe, treatment resistant, OCD patients...
December 1998: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/9871775/dimers-of-5ht1-ligands-preferentially-bind-to-5ht1b-1d-receptor-subtypes
#19
M Perez, C Jorand-Lebrun, P J Pauwels, I Pallard, S Halazy
New dimers of known 5HT1 ligands (5HT, 1-NP or 8-OH-DPAT) have been prepared and evaluated at human cloned 5HT1B, 5HT1D and 5HT1A receptors. Binding experiments show that all these dimers have better affinities at 5HT1B/1D receptors than their corresponding monomeric ligands. Studies of inhibition of the forskolin-stimulated c-AMP formation mediated by the human 5HT1B receptor show that hetero-bivalent ligands [combining an agonist (5HT) with an antagonist (1-NP)] behave as partial agonists while the intrinsic activity of bivalent antagonists (combining two 1-NP residues) was found to be spacer dependent...
June 2, 1998: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/9725544/effect-of-hepatic-impairment-on-the-pharmacokinetics-of-zolmitriptan
#20
COMPARATIVE STUDY
R Dixon, S French, J Kemp, M Sellers, V Leclerc, M Delvaux, J Rautureau
Zolmitriptan, an oral 5HT1D agonist for the acute treatment of migraine, is cleared from the systemic circulation mainly by hepatic metabolism. Consequently, changes in hepatic function may result in changes in the pharmacokinetics of zolmitriptan. This open, parallel-group study was conducted to compare the pharmacokinetics and tolerability of a single 10-mg dose of zolmitriptan in healthy subjects and patients with hepatic impairment. A total of 37 participants entered and completed the study, including 10 healthy volunteers, 11 patients with moderate hepatic impairment, 10 patients with severe hepatic impairment without ascites, and 6 patients with severe hepatic impairment with ascites...
August 1998: Journal of Clinical Pharmacology
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