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Treatment of acute migraine with sumatriptan--response in 40 consecutive patients.

Forty consecutive headache patients self-administered sumatriptan for migraine, diagnosed by the criteria of the International Headache Society (IHS). Eighty percent reported excellent response. Thirty-three percent had recurrence of headache within four to twelve hours, while 67% had no recurrence. Fifty-five percent of the patients reported mild side effects, but only 8% stopped therapy because of adverse reactions. No serious cardiovascular events occurred. Recommendations for safe use of sumatriptan are suggested.

Acute Disease↗

Sumatriptan for post-ECT headache.

A 27-year-old woman receiving electroconvulsive therapy (ECT) for the treatment of depression developed post-ECT headaches refractory to treatment with acetaminophen and various nonsteroidal antiinflammatory drugs. The patient was then treated successfully with oral sumatriptan. This case suggests that sumatriptan may be a useful treatment of post-ECT headaches that are unresponsive to conventional analgesics.

Administration, Oral↗

Postpartum cerebral angiopathy associated with the administration of sumatriptan and dihydroergotamine--a case report.

Cerebral angiopathy of the postpartum period is a rare entity, sometimes promoted by vasoconstrictives drug prescription. Its clinical presentation includes headaches, seizures and focal neurological deficits, which develop shortly after a normal pregnancy. The diagnosis is based on clinical findings and angiography, showing multiple narrowing of the intracranial cerebral arteries. This neurological feature is reversible and the clinical outcome is good. We report a case of benign cerebral angiopathy in a 20-year-old woman in the postpartum period, occurring after administration of sumatriptan and ergot derivates.

Adult↗

Spontaneous splenic infarction associated with sumatriptan use.

Triptans are specific agonists of the serotonergic 5-HT(1B/1D) receptors that have increasingly been used in the treatment of migraine and cluster headaches. Though they are generally considered safe, there have been a few reports of myocardial infarction and stroke associated with triptan use. We report a patient who developed spontaneous splenic infarction after the use of sumatriptan for the treatment of migraine headache.

Causality↗

Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion.

Vasoactive neuropeptides, present in unmyelinated C-fibers, can be released from perivascular sensory axons by antidromic stimulation, to mediate vasodilation and extravasation of plasma protein (neurogenic inflammation). In this report, the effects of antidromic trigeminal stimulation on levels of calcitonin gene-related peptide (CGRP) in plasma were examined in the superior sagittal sinus and the effects of drugs that have been shown previously to block extravasation of neurogenic plasma determined. The levels of immunoreactive CGRP in plasma were measured both before and during electrical stimulation of the trigeminal ganglion (0.1-1.0 mA, 5 msec, 5 Hz, 3-5 min), using a highly specific and sensitive immunochemiluminometric assay. Levels of CGRP increased and became maximal within the first minute of stimulation. The increases were detectable at intensities of current as small as 0.1 mA. Peak levels related to the intensity of the stimulus. Samples from femoral arterial blood did not show concomitant increases at 1 min. Pretreatment with dihydroergotamine (DHE) (50 micrograms/kg i.v.) did not change the baseline levels but decreased levels of CGRP during stimulation (0.3 mA), by 55% at 1 min and 50% at 3 min. Sumatriptan (GR43175) (300 micrograms/kg) attenuated the increase by 57% at 3 min (0.1 mA, 5 msec, 5 Hz) but not after 1 min of stimulation, although decreases were observed at the latter time during an individual experiment. Drug-induced attenuation of levels of CGRP in plasma may reflect inhibition of release, to thereby provide evidence to explain blockade of neurogenic extravasation of plasma.

Animals↗

Differential pulse voltammetric determination of sumatriptan succinate (1:1) in a tablet dosage form.

A voltammetric study of the oxidation of sumatriptan succinate (1:1) has been carried out at the glassy carbon electrode. This compound exhibited a single wave in Britton-Robinson buffer solutions of pH 2-11, with a maximum current at pH 5.0. The mechanism of oxidation was shown to be due to oxidation of the N-H group in the indole ring. Based on this study, a simple, rapid and sensitive voltammetric method was developed for the determination of the drug in a tablet dosage form.

Electrochemistry↗

Sumatriptan provokes coronary artery spasm in patients with variant angina: possible involvement of serotonin 1B receptor.

BACKGROUND: Serotonin (5HT) can induce coronary artery spasm (CAS) in patients with variant angina (VA). We have previously reported that 5HT(1B) and 5HT(2A) receptors gene were expressed in human coronary arterial smooth muscle cells and that isolated coronary artery from a patient with VA showed the supersensitivity to sumatriptan (SMT), a 5HT(1B/1D) receptor agonist. The aim of the present study was to determine whether SMT can provoke CAS directly or indirectly through platelet aggregation in patients with VA. METHODS: We evaluated the effects of intracoronary infusion of graded concentrations of SMT on coronary arteries in 9 patients, including 5 documented VA and 4 participants with atypical chest pain as control. RESULTS: SMT provoked CAS in all patients with VA. SMT could not induce CAS in control. SMT (10(-4) M) caused significant contractions (%diameter of baseline; median [interquartile range], 0 [0-18.4]% in VA, as compared with control (proximal segments; 92.6 [77.9-118.9]%, p<0.05 vs. VA, distal segments; 92.9 [65.3-158.5]%, p<0.01 vs. VA). In control, minor dilation occurred at SMT concentration up to 10(-5) M. SMT could induce in vitro platelet aggregation neither in healthy subjects nor in patients with VA. CONCLUSIONS: These findings suggest that activation of 5HT(1B) receptor by SMT can induce CAS directly in patients with VA without platelet activation. This is the first report directly demonstrating the effect of 5HT(1B) receptor activation on human coronary arteries in vivo.

Adult↗

High-performance liquid chromatographic determination of sumatriptan after in vitro transdermal diffusion studies.

A simple, accurate, precise and rapid HPLC method with UV detection has been validated in order to determine the in vitro transdermal absorption of sumatriptan succinate. The HPLC method is a modification of that described by Nozal et al. [M.J. Nozal, J.L. Bernal, L. Toribio, M.T. Martin, F.J. Diez, J. Pharm. Biomed. Anal. 30 (2002) 285-291]. Separation was carried out on a 250 mm Kromasil C18 column at room temperature. The detector response, at 282.7 nm, was found to be linear in a concentration range between 0.145 and 145 microM. The limit of detection (LOD) was 0.019 microM and the limit of quantification (LOQ) was 0.145 microM.

Administration, Cutaneous↗

Identification of an amino acid residue important for binding of methiothepin and sumatriptan to the human 5-HT(1B) receptor.

Site-directed mutagenesis of the human 5-HT1B receptor was performed to investigate the role of the amino acid residues cysteine 326 and tryptophan 327 in transmembrane region VI and aspartic acid 352 in transmembrane region VII in ligand binding. Binding studies were performed with the antagonist radioligand [3H]GR125743 on mutant and wild-type receptors stably expressed in Chinese hamster ovary cells (CHO)-K1 cells. Substitution of tryptophan 327 by alanine resulted in decreased affinities of all ligands tested. The most prominent changes in affinity were observed for the antagonist methiothepin and the antimigraine drug sumatriptan, which were reduced approximately 300- and 60-fold, respectively. Nevertheless, the affinity of 5-HT remained the same. Replacement of the aspartic acid 352 by alanine reduced high-affinity binding of 5-HT. Substitution of cysteine 326 by alanine had minor effects on ligand binding. Some of these results agree with the results from mutagenesis studies of the corresponding amino acids in other receptors. However, some notable differences also emerge showing that functional roles of individual amino acid residues must be tested experimentally in each receptor subtype.

Amino Acid Sequence↗

Development and validation of an LC assay for sumatriptan succinate residues on surfaces in the manufacture of pharmaceuticals.

A high performance liquid chromatographic (HPLC) method for the assay of sumatriptan succinate residues in swabs collected from manufacturing equipment surfaces was developed and validated in order to control a cleaning procedure. The swabbing procedure using two cotton swabs moistened with water was validated applying a wipe-test and a HPLC method developed to determine low quantities of the drug. The HPLC method involves a C18 column at 25 degrees C, a mixture of ammonium phosphate monobasic (0.05 M)-acetonitrile (84:16, v/v) as a mobile phase and UV detection at 228 nm. Using the proposed method, the average recoveries obtained are of 88.5% for vinyl, 94.2% for glass and 95.2% for stainless steel plates with RSD of 5.5 (n=36), 2.3 (n=36), 2.2% (n=36), respectively. The method was successfully applied to the assay of real swab samples collected from the equipment surfaces.

Chromatography, High Pressure Liquid↗

A method using a liquid chromatographic-electrospray-mass spectrometric assay for the determination of antimigraine compounds: preliminary pharmacokinetics of MDL 74,721, sumatriptan and naratriptan, in rabbit.

MDL 74,721 (I), sumatriptan(II) and naratriptan(III) are new 5-HT1-like agonists that have potential as a novel treatment for migraine. Liquid chromatographic-electrospray-mass spectrometric (LC-ESI-MS) assay have been developed to compare the pharmacokinetics of these three antimigraine compounds. The concentration of each parent drug was determined using a solid-phase extraction method and LC-ESI-MS analysis demonstrating the high sensitivity and specificity of the methods down to subnanogram levels in rabbit plasma samples. Pharmacokinetic parameters evaluated after administration of single intravenous and oral doses were very similar and the ANOVA analysis did not show any statistically significant differences for t1/2, Cmax, V or AUC (normalised). The pharmacokinetic parameters showed short t1/2 (range 1.14-1.9 h) either after intravenous (i.v.) or oral (p.o.) administration and high total body clearance (CL) after the p.o. dose both probably due to extensive and rapid metabolism of the parent drugs as suggested by the low values for bioavailability (range 13.4-22.8%).

Administration, Oral↗

Migraine-like symptoms triggered by occipital lobe seizures: response to sumatriptan.

BACKGROUND: The relationship of ictal and post-ictal cephalic pain to migraine remains debatable. We hereby report 2 patients, a 27-year-old woman and 41-year-old man were referred for assessment of migraine of 10 years and 4 years duration, respectively. The man described a recent episode of "vacant stare" and the woman has sensitivity to bright colours and light. Neurological examination, visual field testing, CAT scan, MRI scan, and prolonged EEG recordings were accomplished for each patient. RESULTS: The man had a spontaneous seizure with ictal discharge arising from the right occipital lobe. Bilateral occipital spikes, associated with palinopsia was triggered in the woman by photic stimulation. Both patients developed post-ictal headaches with symptoms similar to their migraines. The symptoms subsided following treatment with oral sumatriptan. CONCLUSION: Migraine-like symptoms occurring following occipital lobe seizures may share similar pathophysiological substrates with idiopathic migraine. Serotonergic mechanisms may be implicated.

Adult↗

Effect of the 5-HT1 agonist sumatriptan on oesophageal motor pattern in patients with ineffective oesophageal motility.

The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.

Adult↗

From serotonin receptor classification to the antimigraine drug sumatriptan.

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.

Animals↗

Ergotamine-induced headache can be sustained by sumatriptan daily intake.

We describe the case report of a migraine sufferer who developed ergotamine-induced headache and subsequently replaced ergotamine with daily sumatriptan (100 mg p.o.). The features of the headache were unchanged except for the presence of superimposed migraine-like headaches that occurred every 24 h.

Adult↗

Safety trial with the 5HT1B/1D agonist avitriptan (BMS-180048) in patients with migraine who have experienced pressure, tightness, and/or pain in the chest, neck, and/or throat following sumatriptan.

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of all attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients (n = 51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patients, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.

Adult↗

The site of common side effects of sumatriptan.

Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.

Adult↗