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)

A series of single dose studies has been undertaken after intravenous, subcutaneous and oral administration to healthy volunteers to determine safety, tolerability and pharmacokinetics of GR43175, a novel 5-HT 1-like receptor agonist. GR43175 proved to be well tolerated using all routes of administration. Minor side effects were reported including scalp tingling, sensations of bodily warmth, lightheadedness and heavyheadedness. In addition, short-lasting vasopressor effects were encountered, although no drug-related changes were seen in heart rate and ECG or in laboratory safety screens. The drug was rapidly absorbed after oral dosing and had a mean absolute bioavailability of 14% due at least in part to first-pass metabolism. Plasma concentrations in healthy volunteers fell within the range for producing relief of headaches in migraine patients. GR43175 had a high mean plasma clearance (1313 ml/min), the majority of which was due to non-renal clearance and a large volume of distribution (2351). The mean half-lives were 1.7 h and 2.3 h after intravenous and oral doses, respectively.
Cephalalgia 1989
PMID:Early studies with the novel 5-HT 1-like agonist GR43175 in healthy volunteers. 254 85

The novel 5-HT 1-like receptor agonist GR43175 has been evaluated as a treatment for acute migraine in a series of open, dose-ranging and controlled clinical trials. Patients with severe attacks of migraine have attended special pain or headache clinics for treatment and assessment. Given intravenously as a bolus, GR43175 is capable of aborting all migraine symptoms within 10-30 min in over 90% of cases at a dose of 64 micrograms/kg. Characteristic transient and reversible side effects with such a regimen include feelings of heaviness, pressure and occasionally warmth or tingling which can be diminished by extending the duration of drug administration to a short infusion. Initial dose-ranging studies with a dispersible tablet formulation of GR43175 have revealed an efficacy of 70-85% within 2 h with doses of 70-280 mg. Furthermore, tolerability is excellent. These encouraging early results warrant larger-scale controlled studies of GR43175 in acute migraine.
Cephalalgia 1989
PMID:Overview of initial clinical studies with intravenous and oral GR43175 in acute migraine. 254 86

In six European clinics 111 migraine patients were treated in a series of open dose-ranging studies with subcutaneous injections of 1 to 4 mg GR43175, a novel 5-HT 1-like receptor agonist. Response rates after 20-30 min were dose related and rose from 33% with 1 mg to 96% with 4 mg GR43175. Side effects were minor and transient. These promising results warrant confirmation in placebo-controlled double-blind trials. Migraine, treatment, 5-HT agonist, open studies.
Cephalalgia 1989
PMID:Early clinical experience with subcutaneous GR43175 in acute migraine: an overview. 254 87

A subcutaneous preparation of GR43175, a novel antimigraine 5-HT 1-like agonist, was considered to represent a convenient way of administering the drug to patients during an acute migraine attack. In a series of open, uncontrolled dose-ranging studies, 82 patients with migraine were assessed serially for changes in severity of headache and associated symptoms following subcutaneous GR43175 in doses of 1-4 mg. Subcutaneous injection of 3 mg or 4 mg was found to be most effective. Within 60 min, 90% of patients had obtained complete relief of all migraine symptoms. Tolerability was good, 59% of patients reporting no adverse effects. Those reported mainly comprised transient local irritation to the injection. There were no changes attributable to GR43175 in heart rate, blood pressure, ECG readings or laboratory parameters.
Cephalalgia 1989
PMID:Treatment of acute migraine with subcutaneous GR43175 in West Germany. 254 89

GR43175, a selective 5-HT 1-like agonist, was administered as oral dispersible tablets in an open, uncontrolled dose-ranging study to assess its efficacy as an agent for acute migraine. Nine patients, all with well established attacks, were assessed for changes in severity of headache and associated symptoms over 2 h. Drug absorption was compared during and between attacks in five patients. Doses of 140 mg and 280 mg resulted in complete relief of all symptoms within 2 h. Treatment was well tolerated in all patients.
Cephalalgia 1989
PMID:Effective improvement of symptoms in patients with acute migraine by GR43175 administered in dispersible tablets. 254 90

Platelet serotonin (5 hydroxytryptamine, 5-HT) and norepinephrine (NE) were measured in common and classic migraine patients and healthy controls. Common migraine sufferers had high NE levels and a low 5-HT/NE ratio. Classic migraine patients had a high 5-HT level and a high 5-HT/NE ratio. The data suggest disparate NE and 5-HT metabolism between common and classic migraine.
Headache 1989 Nov
PMID:Platelet norepinephrine and serotonin balance in migraine. 261 14

5-Hydroxytryptamine (5-HT, serotonin) is thought to play a part in the pathophysiology of migraine because platelet content of 5-HT in cubital and external jugular veins is reduced during migraine headache. Moreover migraine headache is precipitated by intramuscular injection of reserpine, which releases 5-HT from body stores, is relieved by the intravenous infusion of serotonin, and is prevented by the regular administration of medications that act on 5-HT receptors. Whether the peripheral action of 5-HT on cerebral and extracranial vessels or its central action as a neurotransmitter involved in bulbocortical and pain control pathways is of greater importance in the mechanism of migraine remains an open question. Increasing knowledge of the varieties of 5-HT receptor and the development of pharmacological agents that act specifically on certain receptors should give greater insight into the cause of migraine and increase the efficacy of treatment.
Cephalalgia 1989
PMID:5-Hydroxytryptamine and its putative aetiological involvement in migraine. 266 Oct 13

The functional roles of monaminergic transmitters in depression have been widely studied during the past decade. Data from that research suggest that lower levels of the 5-HT metabolite, 5-HIAA, in the cerebrospinal fluid; 5-HT uptake in human platelets; and platelets [3H]-imipramine binding sites occur in depressed patients. In recent years several potent and selective 5-HT uptake inhibitors have become available for clinical studies. The first shown to have antidepressant effects, zimelidine, was followed by similar compounds such as femoxetine, fluvoxamine, citalopram, indalpine, fluoxetine, paroxetine, and sertraline. The effectiveness of serotonin inhibitors in treating other disorders, such as obsessive-compulsive disorder, anxiety, and panic disorder, has also been demonstrated. This review reports the data from clinical studies with these agents. The 5-HT uptake inhibitors are devoid of anticholinergic properties and have not produced weight gain or sedative side-effects, but may have another profile of side-effects. Headache, nausea, and vomiting have been reported, however.
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PMID:The antidepressant effects of 5-HT uptake inhibitors. 269 38

Pipethiadene, a prophylactic of vasomotoric headaches of the series of 4,9-dihydrothieno(2,3-c)-2-benzothiepine derivatives, shows a peripheralpharmacological profile of an antiallergic agent. The experiments in rats showed a high antianaphylactic effect of pipethiadene in the passive cutaneous anaphylaxis (PCA) test. Pipethiadene also exerted intensive antianaphylactoid action in rats on the liberator of histamine, compound 48/80, on dextran, and in the use of a combination of ovalbumin with indomethacin. In comparative pharmacological experiments with pizotifen and cyproheptadine an attempt was made to estimate the relative role of histamine and 5-hydroxytryptamine 5-HT) mediators in the employed experimental procedures in rats.
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PMID:[Anti-allergic properties of pipethiaden--a new preventive agent for migraine]. 279 Sep 93

Behavioral, physiologic and exertional fatigue is differently defined, though symptoms are similar. The beneficial effect of amantadine on fatiguability in multiple sclerosis is accompanied by neuropeptide and lactate changes in the circulation. Exercise sometimes overwhelms temperature regulating mechanisms and may be associated with heat stroke. Endogenous opioids are markedly increased in the circulation during heat stroke and the use of specific opioid antagonists therapeutically has been proposed for heat stroke. Sympathetic activity changes in endurance trained subjects and vasoconstrictor responses are markedly attenuated. Similar changes occur in parasympathetic function which can be abnormal in up to 90% of endurance trained subjects. Hormonal secretion during prolonged exertion is altered and the normal signals (inhibiting or activating feedback mechanisms) are different in endurance trained subjects. Altitude, associated with acute mountain sickness, is also accompanied by an increase in cranial bloodflow. Circadian and temporal variation in autonomic function are manifest by changes in mast cell numbers and 5-HT containing nerve fibers in temple skin of patients with cluster headache. The remission rate induced by vagal stimulation in subjects with intractable hiccups is also affected by circadian hormonal or neurogenic influences.
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PMID:The autonomic nervous system and fatigue. 296 78


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