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 physiology and pharmacology of the middle meningeal artery was investigated in cats in order to determine whether this artery was subject to normal neural and humoral control mechanisms. Carotid and middle meningeal arterial blood flows and resistances were measured in 16 cats anaesthetized with chloralose. The cervical sympathetic nerves were stimulated electrically. Stimulation of the cervical sympathetic nerves pre-ganglionically reduced blood flow in the middle meningeal artery by producing vasoconstriction in its resistance bed. The vasoconstriction was mediated via catecholamine-containing nerves, as it was abolished by prior intravenous administration of bretylium. Intravenous injections of noradrenaline or adrenaline also produced vasoconstriction in the middle meningeal arterial bed. 5-Hydroxytryptamine (5HT), on the other hand, produced a dilatation in the middle meningeal artery. We conclude that neurally or humorally released catecholamines can provide a plausible mechanism for vasoconstriction in the middle meningeal artery. The dilator effect of 5HT contrasts with the constrictor effect of the 5HT1-like receptor agonist sumatriptan and suggests a complex 5HT receptor pharmacology for the artery.
Cephalalgia 1996 Feb
PMID:Reactions of the middle meningeal artery of the cat to neural and humoral stimulation. 882 96

The involvement of monoamines in the initiation or maintenance of epileptic phenomena has been extensively studied in cerebral tissues and in cerebrospinal fluid. The present work was undertaken to study monoamines and their metabolites in human spiking and non-spiking temporal cortex excised from patients with complex partial seizures unresponsive to available anticonvulsants. The same substances were also analyzed by HPLC-ED in cerebrospinal fluid obtained 24 h before the surgical procedure and compared with those from patients with chronic headache and normal neurological evaluation. The results show increased 5-HT, 5-HIAA and HVA levels in spiking compared with non-spiking cortex. Cerebrospinal fluid levels of 5-HIAA and HVA are concomitantly increased in epileptic compared with headache patients.
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PMID:Monoamines and their metabolites in cerebrospinal fluid and temporal cortex of epileptic patients. 888 71

5-Hydroxytryptamine (5HT), commonly known as serotonin, which predominantly serves as an inhibitory neurotransmitter in the brain, has long been implicated in migraine pathophysiology. This study tested an MspI polymorphism in the human 5HT2A receptor gene (HTR2A) and a closely linked microsatellite marker (D13S126), for linkage and association with common migraine. In the association analyses, no significant differences were found between the migraine and control populations for both the MspI polymorphism and the D13S126 microsatellite marker. The linkage studies involving three families comprising 36 affected members were analysed using both parametric (FASTLINK) and non-parametric (MFLINK and APM) techniques. Significant close linkage was indicated between the MspI polymorphism and the D13S126 microsatellite marker at a recombination fraction (theta) of zero (lod score = 7.15). Linkage results for the MspI polymorphism were not very informative in the three families, producing maximum and minimum lod scores of only 0.35 and -0.39 at recombination fractions (theta) of 0.2 and 0.00, respectively. However, linkage analysis between the D13S126 marker and migraine indicated significant non-linkage (lod < -2) up to a recombination fraction (theta) of 0.028. Results from this study exclude the HTR2A gene, which has been localized to chromosome 13q14-q21, for involvement with common migraine.
Cephalalgia 1996 Nov
PMID:Migraine association and linkage analyses of the human 5-hydroxytryptamine (5HT2A) receptor gene. 893 89

Ramosetron hydrochloride as a 5-HT3 receptor antagonist-type antiemetic, which was developed in Japan. It has an indole ring which is the mother nucleus of serotonin (5-HT) and a tetrahydrobenzimidazol radical. These components are linked by a carbonyl radical. It was reported in non-clinical studies that ramosetron hydrochloride exhibited more potent and sustained antagonistic activities against 5-HT3 receptors than existing 5-HT3 receptor antagonist-type antiemetics. It was also reported that ramosetron hydrochloride inhibited vomiting by anticancer drugs in a potent and sustained manner. The phase I trial was initiated in May, 1991. Phase II and phase III trials were then conducted in a total of 357 patients at 121 institutions in Japan. The symptoms targeted in these trials were nausea and vomiting induced by anticancer drugs, such as cisplatin. Based on the results of the phase II trial, it was recommended that ramosetron hydrochloride be infected once daily at a dose of 0.3 mg. In phase III trial, a placebo-controlled double-blind study and an open trial was performed. The utility of the drug seemed to be confirmed by the results of these studies. Ramosetron hydrochloride shown an efficacy rate of 79.8% (178/223 patients) against nausea and vomiting induced by anticancer drugs, such as cisplatin when administered at a dose of 0.3 mg. The efficacy rate was 85.1% (40/47 patients) when given at a dose of 0.3 mg before the administration of anticancer drugs, such as cisplatin. The incidence of adverse effects was 2.0% (7/352 patients). Main adverse effects reported were feeling of heat, headache, and heavy feeling in the head. These adverse effects were of no clinical importance.
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PMID:[A new antiemetic ramosetron hydrochloride]. 905 Nov 43

Venlafaxine, a phenylethylamine, and nefazodone, a phenylpiperazine compound, are the newest antidepressants to receive approval of the Food and Drug Administration and to be marketed in the United States. Both strongly inhibit serotonin (5-HT) reuptake; venlafaxine also inhibits norepinephrine reuptake, and nefazodone also exhibits 5-HT2-receptor antagonism. Venlafaxine inhibits the cytochrome P-450 2D6 isozyme to a lesser extent than the selective serotonin reuptake inhibitors (SSRIs) and is 27% protein bound. Structurally, the drugs are unrelated to SSRIs and have some clinically important differences in side effect profiles. Nausea, headache, somnolence, and dry mouth are the most frequently reported side effects with both. Sustained hypertension was reported by a limited number of venlafaxine-treated patients.
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PMID:Venlafaxine and nefazodone, two pharmacologically distinct antidepressants. 916 54

Recent PET studies performed in humans during migraine attacks revealed a 'spreading depression-like' oligemia in the occipital cortex during the aura phase and a region of increased blood flow in the brainstem during the headache phase. Animal models were established to test new migraine drugs. A number of 5-HT agonists, the so-called 'triptans', will be available in future besides sumatriptan to treat acute migraine attacks. Migraine prophylaxis is still hampered by the fact that we do not understand the action of drugs used for this purpose and do not have an animal model. Nevertheless, new substances were introduced recently into the prophylaxis of migraine.
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PMID:Emerging treatments in headache. 936 28

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT), which was previously reviewed as an antidepressant in Drugs in 1991. Since then, more comparative trials with other antidepressants have become available, and its use in the elderly and as long term maintenance therapy has been investigated. Paroxetine has also been studied in several other disorders with a presumed serotonergic component, primarily obsessive compulsive disorder (OCD) and panic disorder. In short term clinical trials in patients with depression, paroxetine produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with other agents including tricyclic antidepressants (TCAs), maprotiline, nefazodone and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine and sertraline. Long term data suggest that paroxetine is effective in preventing relapse or recurrence of depression in patients treated for up to 1 year. In the elderly, the overall efficacy of paroxetine was at least as good as that of comparator agents. In short term clinical trials involving patients with OCD or panic disorder, paroxetine was significantly more effective than placebo and of similar efficacy to clomipramine. Limited long term data show that paroxetine is effective in maintaining a therapeutic response over periods of 1 year (OCD) and up to 6 months (panic disorder). Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache. Like the other SSRIs, paroxetine is better tolerated than the TCAs, causing few anticholinergic adverse effects. The most commonly reported adverse event associated with paroxetine treatment is nausea, although this is generally mild and subsides with continued use. Fewer withdrawals from treatment due to adverse effects occurred with paroxetine treatment than with TCAs. The adverse events profile of paroxetine appears to be broadly similar to that of other SSRIs, although data from comparative trials are limited. Serious adverse effects associated with paroxetine are very rare. In conclusion, paroxetine is effective and well tolerated, and suitable as first-line therapy for depression. It also appears to be a useful alternative to other available agents for the treatment of patients with OCD or panic disorder.
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PMID:Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders. 946 92

The past decade has seen significant advances in both the scientific and clinical understanding of migraine. At present, a considerable body of data indicates that migraine is characterized by at least three major pathophysiological features: dopaminergic hypersensitivity, inflammation, and relatively "low" 5-HT levels. Clinically, blocking dopamine receptors, reducing inflammation, and/or stimulating a subpopulation of 5-HT1 receptors are effective monotherapeutic approaches in many migraineurs. However monotherapeutic approaches to migraine do not provide rapid, consistent, and complete relief in all migraineurs. Therefore, if monotherapy is suboptimal, it follows logically that concurrent therapy (ie, polytherapy) aimed at modulating two or three of the biological systems should be more efficacious than modulating only a single system. The rationale for the combination use of dopamine antagonists, anti-inflammatory agents, and 5-HT1 agonists are described in the present report.
Headache 1998 Jan
PMID:Beyond monotherapy: rational polytherapy in migraine. 950 98

Accumulating evidence indicates that serotonin (5-HT) may be involved in the process of analgesic-induced headache transformation. In order to clarify this hypothesis, we investigated the 5-HT system in migraine patients with analgesic abuse headache by using platelets as a neuronal model. Our results revealed a significant decrease in platelet 5-HT content in these patients compared to migraine patients and nonheadache controls (179.24 +/- 10.18, 451.22 +/- 14.35, and 480.22 +/- 13.98 ng/10(9) platelets, respectively; P < 0.001). This biochemical result was well correlated with a significant decrease (P < 0.001) in platelet dense body number observed in these patients (5.9 +/- 0.4 and 9.2 +/- 0.6 granules/10 platelets. For migraine patients with and without analgesic abuse headache, respectively). Beside the 5-HT depletion, the presence of numerous large intracytoplasmic vacuoles formed from the surface-connecting canaliculi system was found in this condition. Such a finding has not been previously described. The total area occupied by these vacuoles was significantly greater (P < 0.01) in migraine patients with analgesic overuse than in migraine patients and nonheadache controls (249.2 +/- 19.5, 164.1 +/- 19.5, and 183.1 +/- 20.3 nm2/cells, respectively). As this canaliculi system plays a significant role in the platelet secretory response, such dilatation may imply an excessive release of substances from this system. Based on this platelet model, we suggest that excessive use of analgesics alters the central 5-HT system by depleting 5-HT from its storage sites and results in the hyposerotonergic state. This analgesic-induced 5-HT alteration may be a possible mechanism of headache transformation observed in this condition.
Headache 1998 Jan
PMID:Derangement of serotonin system in migrainous patients with analgesic abuse headache: clues from platelets. 950 3

Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).
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PMID:Medical treatment of migraine: from mechanisms of action to contraindications. 955 32


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