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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects on the sexual tone of parachlorophenylalanine, a selective inhibtor of 5-hydroxytryptamine synthesis, testosterone and placebo were evaluated in patients complaining of migraine-headache and sexual deficiency. The combined treatment with parachlorophenylalanine and testosterone significantly increases the sexual stimulus more than parachlorophenylalanine, testosterone and placebo, when given on their own. Conversely subjects with normal or excessive sexual activity, reported a decrease of sexual tone, during chronic treatment with tryptophan. The hypothesis of an implication of brain 5-HT in the mechanism of psychogenic sexual deficiency and the possibility of a therapeutic approach with drugs able to interfere with 5-HT turnover are discussed.
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PMID:The influence of tryptophan and parachlorophenylalanine on the sexual activity in man. 14 11

Monoamines are involved in the central nervous assimilation and modulation of the pain flow. According to a personal hypothesis, a disorder of this biochemical control (in particular a precariousness of brain 5-hydroxytryptamine turnover), is the basic mechanism of some painful conditions, such as migraine and other essential headaches. Acute (infusion) and chronic (ingestion) administration of tryptophan to migraine-headache sufferers improved the clinical course significantly in respect to placebo. Few patients with untractable pain from disseminated cancer received daily infusion of tryptophan and ingested a few gr of this amnioacid: improvement of pain and reduction of morphine necessity was observed. Parachlorophenylalanine chronic administration in migraine-headache sufferers lowered the pain threshold so far as to provoke (in 20% of cases) spontaneous pains in the trunk, legs and arms. This systemic pain syndrome was promptly reversible by discontinuing the treatment. Spontaneous pain syndrome was not reported by others in the healthy subject; this suggests an apparent vulnerability of 5HT turnover in essential headaches.
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PMID:5-Hydroxytryptamine and pain modulation in man: a clinical pharmacological approach with tryptophan and parachlorophenylalanine. 14 17

The cerebrovascular concomitants of migraine, initial vasoconstrictriction succeeded by vasodilatation, have long been considered the primary event in the pathogenesis of headache. In recent years, certain physicochemical concomitants of the attack have been identified, all involving blood platelets: these include hyperaggregability, decrease 5-hydroxytryptamine concentration and decreased monoamine oxidase activity. These changes may represent the response to a circulating humoral agent, deriving perhaps from the pulmonary vascular bed. The agent may not only bring about nonspecific damage of the kind described but be responsible for the cerebrovascular changes and stimulation of pain receptors characteristic of the disease. This circulating humoral agent may belong to the prostaglandin family.
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PMID:Cerebrovascular changes in migraine: secondary manifestations of a circulating humoral agent? 29 Jul 40

The hypothesis that pro-inflammatory spasmogens may be generated locally in the vessels of the head by neurohumoral stimuli has been tested using an isolated extracranial vascular bed from the rabbit. No spasmogen release was detected after adenosine triphosphate, histamine, acetylcholine or noradrenaline and was seen rarely after tyramine and 5-hydroxytryptamine. Both sympathetic nerve stimulation and periods of vascular stasis released spasmogen, probably an E-type prostaglandin. The local generation of pro-inflammatory substances by excess sympathetic stimulation and/or vascular stasis might contribute to the development and maintenance of the acute migraine attack.
Res Clin Stud Headache 1978
PMID:Spasmogen release from an extracranial vascular bed evoked by neurohumoral stimuli and periods of vascular stasis. 72 55

The blood levels of free tryptophan, glucose and insulin were determined in different groups of patients suffering from headache, initially and after a glucose tolerance and a tolbutamide tolerance test. The control group consisted of subjects without neurological or psychiatric disturbance. A sharp drop of blood tryptophan levels was observed in migraine patients during the tolbutamide tolerance. Migraine attacks may be induced in certain subjects by a disturbance of 5-hydroxytryptamine turnover.
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PMID:Insulin secretion in migraine: influence on the blood levels of tryptophan. 97 99

Experiments were carried out in order to further delineate the pathophysiology of the fall of plasma 5-hydroxytryptamine (5-HT) during a migraine attack. Platelets from normal subjects were incubated with 14C-labelled 5-HT, and the release of 5-HT was measured following exposure of these platelets to plasma taken from migraine patients during an attack or at headache-free intervals. Plasma taken during attacks released significantly more 5-HT. It is concluded that factor(s) exist in the serum during migraine attacks, which can cause 5-HT release from normal platelets. The identification of this factor may be important.
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PMID:Release of platelet 5-hydroxytryptamine by plasma taken from patients during and between migraine attacks. 102 4

After the synthetic serotonin 5-hydroxytryptamine (5-HT) became available in the early 1950s, attempts were soon under way to study the nature of 5-HT receptors. Using the guinea-pig isolated ileum, Gaddum and Picarelli (1957) suggested that 5-HT-induced contractions were mediated by a morphine-sensitive "M" receptor located on the parasympathetic ganglion and a dibenzyline-sensitive "D" receptor located on the smooth muscle. Though this classification ws used during the next three decades, it was realized that some effects of serotonin, for example vasoconstriction within the carotid vascular bed, were not mediated by either "M" or "D" receptors. When radioligand binding studies led to the identification of 5-HT1 and 5-HT2 "receptors" in the rat brain membranes, it became increasingly apparent that the two receptor classifications were not identical. Thus, a new framework for serotonin receptor nomenclature and classification was proposed: 5-HT1-like (5-HT1), 5-HT2 (formerly "D") and 5-HT3 (formerly "M") receptors. At the present time, several subtypes of 5-HT1 receptors as well as a 5-HT4 receptor are also recognized. As the serotonin receptor classification was emerging to indicate that carotid vasoconstriction by serotonin is mediated by a subtype of 5-HT1 receptors, on the migraine front it was being suggested that the disease is associated with vasodilation within the cranial extracerebral circulation and deranged serotonin metabolism and that certain antimigraine drugs caused a selective carotid vasoconstriction, probably via serotonin receptors. Therefore, Humphrey and colleagues conceived that synthesis of serotonin derivatives may lead to a compound that would elicit highly selective carotid vasoconstriction and abort migraine attacks. Indeed, via the synthesis of 5-carboxamidotryptamine and AH25086, sumatriptan was designed. The drug acts as an agonist at the vasoconstrictor 5-HT1 receptor subtype and has proved highly effective in the therapy of migraine attacks.
Cephalalgia 1992 Aug
PMID:From serotonin receptor classification to the antimigraine drug sumatriptan. 132

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.
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PMID:[The role of serotonin in the pathophysiology of migraine]. 133 65

There is little dispute that a link exists between 5-hydroxytryptamine (5HT) and migraine but the exact mechanism of an attack has yet to be established. The handling of 5HT by the platelet is regarded as a simple model of the handling of 5HT by nerve terminals. If differences are seen in how the platelets from migraineurs handle 5HT compared to those from a control population, it is possible that a similar difference exists in the nerve terminal. The Haemostatometer allows the rapid and simultaneous in vitro assessment of platelet function (shear-induced haemostasis), coagulation and thrombolysis from non anticoagulated blood samples. In this study, a baseline comparison of haemostasis was made on 20 migraineurs between attacks and 20 controls. No differences were found in the results from each of the two groups. 5 microM of 5HT was then added to blood taken from 10 migraineurs and 10 controls and the recordings were repeated. Again, no differences were found between the results from the two groups. In blood taken from both migraineurs and controls, the effect of 5HT was to significantly enhance clotting time and clot lysis. No effect was seen on primary aggregation. The possible reasons for and significance of these findings is discussed.
Headache 1992 Jun
PMID:Handling of 5-hydroxytryptamine by platelets in migraine. 139 53

A double-blind, placebo-controlled multicentre study was carried out to evaluate the efficacy and tolerability of 100, 200 and 300 mg sumatriptan, a selective 5-hydroxytryptamine (5-HT)1-like receptor agonist, given in an oral dispersible form in the acute treatment of migraine attacks. A total of 1130 patients were recruited from 51 centres in eight countries and the efficacy results are presented from an interim analysis of 538 cases. Tolerability was evaluated in 227 patients. At 2 h, an improvement in headache severity from moderate or severe to mild or none was reported by 67% of patients who received 100 mg sumatriptan, 75% receiving 200 mg and 69% of patients receiving 300 mg sumatriptan, compared with 22% of patients who received placebo (P less than 0.001 all doses sumatriptan vs placebo). Adverse events were generally mild and transient, and appeared to be dose-related; the adverse event profile of 100 mg sumatriptan was similar to that of placebo. Overall, nausea/vomiting and "bitter taste" were the most common complaints. The proportion of patients withdrawn due to adverse events was similar in the placebo and 100 mg sumatriptan treatment groups (2% and 3%, respectively). It is concluded that 100 mg sumatriptan given orally is well tolerated with an anti-migraine efficacy comparable to that provided by the two higher doses.
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PMID:Clinical experience with oral sumatriptan: a placebo-controlled, dose-ranging study. Oral Sumatriptan Dose-defining Study Group. 164 90


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