Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of the many factors that have been implicated in the pathophysiology of migraine, none seems to have a better claim than serotonin (5-hydroxytryptamine, 5-HT). The evidence for this is: 5-HT concentrations in blood increase during the prodromal (aura) phase and subsequently, decrease to subnormal levels in the headache phase; migraine attacks may be triggered, in susceptible, subjects, by reserpine which depletes body serotonin; migraine attacks may be triggered, in susceptible subjects, by reserpine which depletes body serotonin; migraine attacks may be relieved by intravenous injection of 5-HT; medications known to affect 5-HT concentrations have been shown to be efficacious in both aborting (agonists of 5-HT1 receptors) and preventing (antagonists of 5-HT2 receptors) migraine attacks. Since most of 5-HT in blood is stored in the platelets, attention of many investigators focused on the platelet function abnormalities. The positive findings provoked some of them to hypothesise that migraine is a primarily platelet disorder. Advances in the understanding of the role of 5-HT in migraine and the pharmacology of this amine have now resulted in the development of a highly selective 5-HT1 -like receptor agonist which selectively constricts cranial blood vessels and inhibits neurogenically-mediated plasma protein extravasation in the dura mater.
 ...
PMID:[The role of serotonin in the pathophysiology of migraine]. 133 65

It is well established that cluster headache shows impaired functions at their neuroimmunomodulatory system level. Defect in receptor expression for 5-HT, IL-1 and IL-2 have been found in these patients. Sumatriptan, a molecule with agonistic activity for 5-HT1D receptor, truncates cluster headache attacks in 74% of patients. Flow cytometric analysis of monocytes expressing 5-HT receptor in cluster headache patients showed different trends clearly correlated with the clinical response to sumatriptan. Our findings strongly support the concept that cluster headache patients who are non responders to sumatriptan could present a block in their 5-HT receptor possibly due to specific autoantibodies for this receptor site.
 ...
PMID:[The cluster headache: a clinical model of immunologic receptor pathology?]. 133 21

Neurogenic inflammation has been proposed as a possible pathogenetic mechanism for migraine and cluster headache. Antidromic stimulation of trigeminal fibers causes plasma protein extravasation, mast cell activation and degranulation, vacuolation and increase in endothelial vesicle number within post capillary venules in rat dura mater. The antimigraine drugs sumatriptan and dihydroergotamine block the development of plasma extravasation and ultrastructural changes, as well as plasma calcitonin gene-related peptide (CGRP) increase in the superior sagittal sinus following electrical trigeminal ganglion stimulation. Sumatriptan and dihydroergotamine bind with high affinity to the 5-HT1D/1B receptors, thus suggesting that their neurogenic antiinflammatory activity is mediated by activation of 5-HT autoreceptors present on sensory fibers innervating blood vessels in dura mater.
 ...
PMID:The trigemino-vascular system and migraine. 137 7

We have previously reported that the serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) induced late occurring migraine-like headaches in a group of patients with eating disorders and controls (n = 52). In this report, we extend our analyses of these data and describe results indicating that headache responses following m-CPP are greater in patients with bulimia nervosa than controls, regardless of the presence of anorexia nervosa or major depression. Although patients with severe migraine-like headaches had higher peak m-CPP levels than patients without severe headaches, these levels are not higher than other groups studied who did not get headaches. These findings suggest that post-synaptic 5-HT receptor sensitivity is altered in the vascular tissues of bulimic patients. Additional disturbances in 5-HT function, perhaps presynaptic ones, may be associated with anorexia nervosa and major depression. Similar alterations in other 5-HT pathways at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms of bulimia nervosa. Further studies exploring the functional integrity of 5-HT receptors and their subtypes are warranted in bulimic patients, as well as in patients with nonbulimic anorexia nervosa, minor and major depression without an eating disorder, and migraine and other headache patients.
Headache 1992 May
PMID:Headache responses following m-chlorophenylpiperazine in bulimics and controls. 162 57

The serotonin (5-hydroxytryptamine, 5-HT) antagonists, which bind at the type 3 receptor (5-HT3 receptor), have been evaluated in several preclinical models and found to be effective in alleviating cancer therapy-related emesis. The antiemetic efficacy of ondansetron (GRF-38032F, odanserin), granisetron (BRL-43694), tropisetron (ICS-205930), MDL-72222 and MDL-73147EF, batanopride (BMY-25801-01) and several others is at various stages of investigation. Ondansetron is currently marketed in several countries and the same will soon be true for granisetron. At this stage it is not yet possible to evaluate the comparative efficacy of each of these compounds, although recent preclinical data reveal some differences in the affinity of these compounds, for other receptors. Side effects related to these agents have been minor, consisting mainly of slight headaches; possible rises in liver enzymes related to some compounds need further evaluation. Future studies will need to determine the exact role of 5-HT3 antagonists, although their cost may confine their use to patients at high risk for side effects from metoclopramide.
 ...
PMID:5-HT3 receptor antagonists. An overview of their present status and future potential in cancer therapy-induced emesis. 172 61

The efficacy and tolerability of the selective 5-HT reuptake inhibitor fluvoxamine were compared with the tricyclic dothiepin in 52 elderly (age greater than 64 years) hospital patients in a multi-centre double-blind randomised trial. Patients met DSM-III criteria for 'major depressive episode' and scored greater than 29 on the Montgomery Asberg Depression Rating Scale (MADRS) after a one-week placebo baseline. Active treatment was for six weeks. The dosage of both drugs was 50 mg nocte for three days, 100 mg nocte for the remainder of the first week, thereafter increasing to a maximum of 200 mg/day according to response/tolerance. MADRS scores improved by 63.5% with fluvoxamine and 60.0% with dothiepin; there were no significant differences between treatments at any assessment. Nausea, dizziness, headache, somnolence and constipation in both groups, plus dry mouth and asthenia in the dothiepin group were more frequent than single reports. Two patients in each group discontinued treatment owing to unwanted effects. There were no clinically significant changes in haematological, biochemical or cardiovascular parameters.
 ...
PMID:A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients. 181 Mar 58

Serotonin (5-Hydroxytryptamine) seems to play a dominant role in triggering vomiting induced by cytotoxic agents through the stimulation of 5-HT3 receptors. They have been observed in the GI tract as well as in the brain (area postrema). Ondansetron is a specific antagonist of 5-HT3 serotonin receptors. Its anti-emetic activity is very powerful in the ferret. The availability of an injectable or oral form of this product allows the overall treatment of acute and delayed emesis and its administration is in accordance with different schedules: single IV injection or a continuous 24 hour infusion or repeated IV injection followed by oral treatment. The pharmacokinetics of the drug are as follows: absorption begins about 30 minutes after the administration per os, its biodisponibility is about 60%, its clearance: 20 ml/minute and its elimination half life about 3 hours. Different double blind studies, carried out in parallel groups or in cross over, demonstrated the superiority of ondansetron over metoclopramide in the control of nausea and vomiting, whether or not the chemotherapy contained cisplatin; a more recent study shows also that ondansetron was superior to alizapride and methylprednisolone in combination. Side effects of ondansetron do not include extrapyramidal symptoms but only headaches and constipation. The use of ondansetron improves the well-being of patients receiving chemotherapy and increases protocol compliance.
 ...
PMID:[Ondansetron: a specific 5-HT3 serotonin receptor inhibitor, a new antiemetic in oncology]. 183 90

Using fluorescence histochemistry, 5-HT, histamine and heparin were colocalized in a large population of cells in the dura mater thereby identifying them as mast cells. In addition, because these cells were highly sensitive to compound 48/80 and were densely packed with granules of a consistent density, they were identified specifically as 'connective tissue' mast cells. Other types of mast cells, i.e. 'mucosal' or 'neurolipomastocytes', were not present in the rat dura mater. 5-HT immunohistochemistry was the best technique for demonstrating that there were populations of mast cells, one associated with each of the two layers of dura. Although shaped differently the type of mast cell in each layer was the same. It was observed that mast cell shape is dependent on the contiguity, density and orientation of its surrounding elements, not its type. In general, mast cells in the outer layer were aligned parallel to the middle meningeal artery and those in the inner layer were parallel to trigeminal nerve branches that coursed obliquely across the middle meningeal artery. Examination of cross-sections of dura revealed that most mast cells also were aligned at the interface between the two dural layers. The linear orientation of mast cells in two planes of each layer suggests a programmed lamellar seeding of these cells during development of the dura. This study also demonstrated that the majority of dural mast cells were more closely related to other connective tissue elements than to blood vessels and nerves. These results (1) are compatible with the suggestion that dural mast cells play a non-obligatory role in the neuroinflammatory response, (2) leave open to question the role of the dural mast cell in headache or the regulation of blood flow, and (3) support evidence that dural mast cells play an important role in connective tissue related functions, e.g. development, inflammatory response to injury and wound repair.
 ...
PMID:Linear arrays of homogeneous mast cells in the dura mater of the rat. 186 85

In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache.
 ...
PMID:[Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes]. 190 20

In those subjects genetically susceptible to migraine, biological rhythms or excessive afferent stimulation trigger an episodic neurovascular reaction with focal neurological symptoms, headache and nausea as its most common manifestations. Mood changes and a craving for sweet foods point to a preliminary hypothalamic disturbance. The referral of ice-cream headache and ice-pick pains to the habitual site of migraine headache (even in the intervals between attacks) indicate defective control of trigeminal pathways. Laboratory experiments have demonstrated that projections from the brainstem, releasing monoamines and peptides as transmitter agents, can mimic the vascular changes of migraine. Serotonin released from platelets may sensitize vessels to respond to distension by generating pain-producing afferent discharges. Central depletion of monoamines can accentuate the perception of pain by reducing the efficacy of the endogenous pain control system. The intravenous injection of serotonin relieves migraine headache but produces side-effects. A new drug, sumatriptan, acting on a subtype of serotonin receptors, the 5HT1-like receptor, is undergoing clinical trial for the relief of acute attacks of migraine. Antagonist of the 5HT2 receptor are beneficial in interval therapy for the prevention of migraine. Increased knowledge of physiological mechanisms and neurotransmitters that can mediate the various components of the migraine attack opens the way for improvements in pharmacotherapy.
 ...
PMID:[Physiopathology of migraine]. 196 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>