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

The interactions of four abortive anti-migraine agents and four prophylactic anti-migraine agents with 5-HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti-migraine agents (i.e. 5-hydroxytryptamine, ergotamine, dihydroergotamine, sumatriptan) for 5-HT1D receptors range from 4.0-34 nM while the affinities of prophylactic anti-migraine agents (i.e. methysergide, amitriptyline, (-)propranolol, verapamil) range from 46-11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti-migraine agents dose-dependently inhibit forskolin-stimulated adenylate cyclase activity, a biochemical effect mediated by 5-HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti-migraine agents. These data support the hypothesis that abortive anti-migraine agents are 5-HT1D receptor agonists and that this effect may underlie their anti-migraine efficacy.
Headache 1991 Apr
PMID:5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy. 164 76

In a randomized single-blind international multicentre trial, two antiemetic regimens were compared in 115 oncology patients undergoing chemotherapy for the first time (cisplatin greater than 15 mg/m2, or ifosfamide greater than 1200 mg/m2 or etoposide greater than 120 mg/m2). One group received granisetron, a 5-hydroxytryptamine type-3-receptor antagonist, 40 micrograms/kg alone intravenously before chemotherapy, with, if necessary, up to two further doses daily of 40 micrograms/kg. The second group received a combination of alizapride plus dexamethasone (4 mg/kg alizapride and 8 mg/kg dexamethasone before chemotherapy, repeated, if necessary, after 4 and 8 hours up to two additional doses). There was good antiemetic efficacy (a maximum of one episode of vomiting in 24 hours = "major efficacy") in 50 of 62 patients (80.7%) in the granisetron group, and in 37 out of 53 (69.8%) of those treated with alizapride and dexamethasone; failure of antiemetic therapy occurred in 4.8% (granisetron) and 15.1% (combination) of patients. For the first day of each 5-day chemotherapy cycle, there was a higher rate of excellent antiemetic efficacy (no or only mild nausea, and no vomiting) with granisetron (90.3% vs 69.8%, P less than 0.006). The frequency (29% vs 32%) and nature of side effects (obstipation, diarrhoea, headaches, anxiety, vertigo), the causes of which were not differentiated, were similar. No extrapyramidal reactions occurred with granisetron. Of the 62 patients treated with granisetron, 47 did not require any further granisetron after the single daily prophylactic dose.
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PMID:[Comparison of the antiemetic effectiveness of granisetron and alizapride plus dexamethasone in cytostatic therapy]. 165 80

Progress in migraine research has been rapid in recent years, from both the basic science and the clinical perspectives. A new internationally accepted headache classification with operational diagnostic criteria was published in 1988, eliminating much diagnostic uncertainty. More than a decade of study of regional cerebral blood flow (rCBF) has gradually shown a pathognomonic pattern of abnormalities, probably reflecting spreading cortical depression. Recently it has been shown that pain probably arises from excitation of perivascular pial arterial nociceptors. The innervation and receptor mechanisms of pial and extracranial arteries have been worked out in detail both in animal and humans. Involvement of calcitonin gene-related peptide (CGRP) and 5-hydroxytryptamine (5-HT) during migraine attacks has been demonstrated. A new and specific 5-HT1D receptor agonist has proved to be highly effective in treating migraine. Therefore, major research efforts recently have been concentrated on discovering the location and function of 5-HT1D receptors, extra- and intracranially. Thus, it is now possible to formulate useful neuroscientific research strategies aimed at clarifying migraine mechanisms.
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PMID:Migraine: a research field matured for the basic neurosciences. 170 30

The algesic effect of substance-P with and without the addition of bradykinin or 5-hydroxytryptamine was studied in 13 healthy volunteers. Test substances dissolved in saline were injected into the temporal muscle and the forearm skin and the effects compared with those of saline. In the temporal muscle, none of the test substances induced more pain than saline, but substance-P with bradykinin lowered the pressure pain threshold by 18% (p less than 0.02). All test substances induced pain wheal and flare in the forearm skin. Substance-P induced a more pronounced flare reaction than bradykinin, whereas the latter induced more pain than substance-P. This dissociation between pain and flare may indicate that C-fibres in the human skin represent more than one type of nociceptor.
Cephalalgia 1991 Sep
PMID:Pain, tenderness, wheal and flare induced by substance-P, bradykinin and 5-hydroxytryptamine in humans. 172 Jul 8

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.
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PMID:5-HT3 receptor antagonists. An overview of their present status and future potential in cancer therapy-induced emesis. 172 61

Some cellular immune functions are impaired in cluster headache patients. Interleukin-2 (IL-2) is a polypeptide secreted by antigen or mitogen-actuated T lymphocytes that functions as a growth factor for T cells. To investigate cellular immune functions in patients with chronic headache, we measured the IL-2 concentration of sera in patients with migraine and in patients with tension-type headache. Thirteen subjects suffering from migraine without aura (5 males and 8 females, mean age: 32.8 years) and 46 subjects (20 males and 26 females, mean age: 39.7 years) with tension-type headache (TH) were selected for this study. Forty-three normal healthy volunteers composed the control group (15 males and 28 females, average age 41.6 years). The IL-2 levels of sera were determined using enzyme-linked immunosorbent assay (ELISA) techniques. The IL-2 levels of sera were 3.18 +/- 1.8 U/ml (mean +/- SD) in the healthy controls, 2.29 +/- 2.6 U/ml in the patients with migraine and 1.59 +/- 1.0 U/ml in the patients with TH. The serum level of IL-2 in the patients with migraine was significantly lower than in the controls. The serum level of IL-2 in the patients with TH was significantly lower than in the controls. The central nervous system (CNS) has been considered to be involved in the development of the immune phenomena. In the patients with TH or migraine, reduction in platelet 5-hydroxytryptamine (5-HT) levels and sympathetic hypofunction have been observed. These phenomena might reflect decrease in 5-HT levels in CNS in the patients with TH or migraine. The decreased serum IL-2 level, observed in this study, might reflect a reduction in 5-HT or catecholamine levels in CNS in the patients with migraine or TH.
Headache 1991 May
PMID:Decreased serum interleukin-2 level in patients with chronic headache. 186 Jul 89

Platelet 5-hydroxytryptamine (5-HT) is diminished during migraine headache and the injection of reserpine, which releases 5-HT from body stores, induces a typical headache in migrainous subjects. The intravenous injection of 5-HT relieves established migraine headache, but causes side-effects of nausea, faintness, paraesthesia and dyspnoea. The 5-HT1-like agonist sumatriptan exerts the beneficial effects of 5-HT with minimal side-effects. Receptors for 5-HT are present in cranial arteries and are also widely distributed in the central nervous system, where they play a role in the neural control of the cranial circulation and endogenous pain control system. The pathophysiology of migraine involves interaction between these central pathways and cranial blood vessels. It is probable that many prophylactic agents exert their action by central 5-HT2 antagonism, whereas termination of an established attack of migraine depends upon constriction of cranial vessels mediated by 5-HT1 receptors.
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PMID:5-Hydroxytryptamine and its role in migraine. 188 18

Platelet 5-hydroxytryptamine (5-HT) uptake was measured in asymptomatic headache patients attending a specialist migraine clinic, and in hospital staff who did not suffer from regular or severe headache. Current levels of anxiety and depression were assessed in all subjects using the Hospital Anxiety and Depression (HAD) scale and their possible influence on the uptake kinetics taken into account during the analysis of results. The Michaelis-Menten constant (Km) was significantly raised in common migraine and tension headache compared with controls (p less than 0.001 and p less than 0.01, respectively), but not in classical migraine or cluster headache. The increase remained significant after adjusting for differences in age, sex, presence of anxiety or depression (HAD sub-scale score greater than or equal to 8), drug intake during the week before testing, time elapsed since last attack and time of assay (am or pm). No differences were observed between patients and controls in the maximal rate of uptake (Vmax) or platelet count, and previous reports of a reduction in Vmax in patients experiencing attack within 5 days prior to testing could not be confirmed. The cause and significance of an increased Km are not clear, but plasma factors acting as competitive inhibitors for the uptake site or an alteration in the configuration of the uptake site are possible explanations. If confirmed, the shared biochemical abnormality may suggest that common migraine and tension headache have a common pathogenesis.
Cephalalgia 1991 Jul
PMID:Kinetics of platelet 5-hydroxytryptamine uptake in headache patients. 188 70

Recently there have been reports that long-term use of estrogen- containing oral contraceptives (OCs) can induce folic acid and vitamin B deficiency which can lead to hematopoiesis. The symptoms are paleness, forgetfulness, sleeplessness, and euphoric and depressive states. This deficiency occurs when serum folic content falls below 8 nmol/1 or 3 ng/ml. According to a nutrition group blood folic acid level declined up to 40% in patients taking OCs. In a Sri Lanka study of healthy women aged 20-45 taking Ovulen 50 (.05 mg of ethinyl estradiol and 1 mg of ethynodiol diacetate) folic acid level dropped in the 1st 6 months stabilizing at 2.2 ng/ml in those from the lowest social classes and at 2.9 ng/ml in those from privileged classes. Prophylactic substitution of folic acid in the diet was recommended by WHO, but it is less effective since it appears in the diet as polyglutamate that has to be broken down to absorbable monoglutamate. A US study found that taking OCs for 60 months resulted in a 40% reduction of the vitamin B12 serum level, while vitamin B12 concentrations in erythrocytes and peripheral blood stayed normal. Vitamin B12 helps recover tetrahydrofolic acid from N-methyltetrahydrofolic acid. Possibly this is another manifestation of OC-induced folic acid hypovitaminosis. OCs can also influence tryptophan metabolism reducing its blood concentration whereby less 5-hydroxytryptamine (serotonin) is produced. This results in headache, concentration decreases irritability, and sleep disturbances. In addition, lower riboflavin (vitamin B2) and thiamin concentration in erythrocytes was reported after using OCs. Counseling on the possible effect on vitamin stores and on proper nutrition including folic acid as monoglutamate is necessary for women who use OCs or estrogen substitution therapy for postmenopause or for osteoporosis prophylaxis.
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PMID:[Folic acid and vitamin deficiency caused by oral contraceptives]. 192 42

The results of recent investigations designed to elucidate the neuroeffector functions of sensory fibres, the cause of migraine headache and the mechanism of action of antimigraine drugs are reviewed and discussed. Neurogenic inflammation (vasodilatation and neurogenic plasma extravasation) is one explanation for the development of headaches and the blood flow changes which occur during migraine headache. Numerous studies have recently been carried out on rats and guinea-pigs into the effects of antimigraine agents, including ergot alkaloids, sumatriptan and non-steroidal anti-inflammatory drugs (NSAIDs), on neurogenic plasma protein extravasation in the dura mater induced by electrical stimulation of trigeminal ganglia or systemic administration of capsaicin. It is known that the dura mater is able to produce headaches in man. Ergot alkaloids have been shown to block neurogenic inflammation via a C-fibre dependent neuronal mechanism. Sumatriptan appears to act fairly similarly although, whereas the ergot alkaloids are non-selective for either 5-hydroxytryptamine (5-HT; serotonin) receptors or 5-HT1, sumatriptan is selective for 5-HT1 receptors. The antimigraine action of NSAIDs may be via either an effect on blood vessels or an effect on the nerve fibre. The antimigraine effects of ergot alkaloids, sumatriptan and NSAIDs are discussed in the light of the common vasoconstrictor actions of these agents and knowledge that vasodilatation is apparently not responsible for migraine headache pain in most cases.
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PMID:Neuroeffector functions of sensory fibres: implications for headache mechanisms and drug actions. 204 26


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