Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Sumatriptan”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1998

Validation of a liquid chromatographic tandem mass spectrometric method for the determination of sumatriptan in human biological fluids.

A liquid chromatographic tandem mass spectrometric method for the quantitative determination of sumatriptan base in human plasma and urine has been developed and validated over the concentration range 0.2-20 ng base ml-1. Sumatriptan is a 5-HT1 receptor agonist which has found widespread use in the treatment of migraine. Sumatriptan and its internal standard (D3-sumatriptan) were extracted from human matrices using C2 solid phase cartridges. The extracts were chromatographed on a C18 column, ionised using a heated nebuliser assisted atmospheric pressure ionisation (API) interface and detected by MS/MS in the multiple reaction monitoring mode. The completed validation demonstrated the method to be robust, accurate, precise and specific for the direct quantification of sumatriptan in human fluids. The method was used on a routine basis to determine the levels of sumatriptan in human volunteers following the oral administration of a 25 mg dose of sumatriptan succinate.

Chromatography, Liquid↗
PubMed2000

Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5-HT(1F) receptor agonists and PGF(2alpha).

Contractile responses to ergotamine, sumatriptan and the novel 5-HT(1F) receptor agonists, LY334370 and LY344864 were examined using the rabbit saphenous vein. Ergotamine (pEC(50)=8.7+/-0.06) was 30 fold more potent than 5-hydroxytryptamine (5-HT) (pEC(50)=7.2+/-0.13) and 300 fold more potent than sumatriptan (pEC(50)=6.0+/-0.08) in contracting the rabbit saphenous vein in vitro. The selective 5-HT(1F) receptor agonists, LY334370 or LY344864 (up to 10(-4) M), did not contract the rabbit saphenous vein. The contractile response to ergotamine in this tissue resulted from activation of both alpha(1) and 5-HT(1B/1D) receptors based on the observation that prazosin (10(-6) M), an alpha-adrenoceptor antagonist, and GR127935 (10(-8) M) a 5-HT(1B/1D) receptor antagonist, dextrally shifted the contractile response to ergotamine. In contrast, prazosin (10(-6) M) did not alter contraction to sumatriptan whereas GR127935 (10(-8) M) was a potent antagonist (-log K(B)=10.0) suggesting that sumatriptan-induced contraction of the rabbit saphenous vein was mediated only by activation of receptors similar or identical to 5-HT(1B/1D) receptors. PGF(2alpha) (3x10(-7) M) produced a modest increase (approximately 5.0 - 10.0% maximum PGF(2alpha) contraction) in saphenous vein force. Precontraction with PGF(2alpha) (3x10(-7) M) dramatically augmented the potency and maximal contractile response to sumatriptan (pEC(50)=7.1) and modestly enhanced the contractile potency of ergotamine (pEC(50)=9.0) in the rabbit saphenous vein. However, PGF(2alpha) (3x10(-7) M) only unmasked a contraction to the 5-HT(1F) receptor agonists when concentrations exceeded 10(-5) M, concentrations considerably higher than their 5-HT(1F) receptor affinities. LY334370 (10(-6) M) pretreatment did not alter contraction to either sumatriptan or ergotamine and a higher concentration (10(-5) M) of LY334370 or LY344864 inhibited contraction to sumatriptan. Thus, activation of 5-HT(1F) receptors will not induce vascular contraction (either alone or following modest tone with PGF(2alpha)) or augment contraction to other contractile agonists in the rabbit saphenous vein.

Animals↗
PubMed2001

Sumatriptan elicits both constriction and dilation in human and bovine brain intracortical arterioles.

1. Little is known about serotonin (5-HT) receptors present on brain microvessels that are innervated by brainstem serotonergic neurons. Using 5-HT, sumatriptan and subtype selective 5-HT(1) receptor agonists and/or the 5-HT(1) receptor antagonist GR127935, we characterized the 5-HT receptors involved in regulating microvascular tone of pressurized intracortical arterioles (approximately 40--50 microm) isolated from human and bovine cerebral cortex. The role of nitric oxide (NO) on these responses was assessed with the N(omega)-nitro-L-arginine (L-NNA, 10(-5) M), an inhibitor of NO synthesis. Bovine pial arteries were studied for comparative purposes. 2. At spontaneous tone, 5-HT induced a dose-dependent constriction of human and bovine microarteries (respective pD(2) values of 7.3+/-0.2 and 6.9+/-0.1); a response potently inhibited by GR127935 (pIC(50) value of 8.5+/-0.1) in bovine microvessels. 3. In both species, the 5-HT(1) receptor agonist sumatriptan induced a biphasic response consisting of a small but significant dilation at low concentrations (1 and/or 10 nM) followed by a constriction at higher doses (pD(2) for contraction of 6.9+/-0.1 and 6.6+/-0.2 in human and bovine vessels, respectively). Pre-incubation with L-NNA abolished the sumatriptan-induced dilation and significantly shifted the dose-response of the constriction curve to the left. In contrast, the selective 5-HT(1D) (PNU-109291) and 5-HT(1F) (LY344864) receptor agonists were devoid of any vasomotor effect. 4. In bovine pial vessels, 5-HT and sumatriptan elicited potent constrictions (respective pD(2) of 7.2+/-0.1 and 6.6+/-0.1), a weak dilation being occasionally observed at low sumatriptan concentrations. 5. A significant negative correlation was observed between pial and intracortical vessels diameter and the extent of the dilatory response to 10(-9) M sumatriptan. Together, these results indicate that sumatriptan, most likely via activation of distinctly localized microvascular 5-HT(1B) receptors, can induce a constriction and/or a dilation which is sensitive to inhibition of NO synthesis and dependent on the size and, possibly, the existing tone of the vessels.

Animals↗
PubMed2000

Comparison of the vasoconstrictor effects of the selective 5-HT1D-receptor agonist L-775,606 with the mixed 5-HT1B/1D-receptor agonist sumatriptan and 5-HT in human isolated coronary artery.

AIMS: Vasoconstriction in human coronary artery can be mediated via activation of both 5-HT2 and 5-HT1B-receptors. Coronary vasoconstriction is a rare, but potential adverse effect of the antimigraine drug sumatriptan. In order to investigate the receptor population involved we compared the vasoconstrictor effects of sumatriptan (a mixed 5-HT1B/1D-receptor agonist) with those of L-775, 606 (a selective 5-HT1D-receptor agonist) and 5-HT (the endogenous ligand) in human isolated coronary arteries. METHODS: Coronary arteries were obtained from human hearts removed prior to transplant surgery. Several endothelium denuded ring segments (4 mm in length) were obtained from each artery and mounted for isometric tension recording. Each segment was first exposed to 45 mm KCl and then to 5-HT (1 nm-100 microm ). Concentration-effect curves to L-775,606 (1-(3-(5-(1,2, 4-triazol-4-yl)-1H-indol-3-yl)propyl)-4-(2-(3-fluorophenyl)ethyl)p ipe razine) and sumatriptan were then performed in a consecutive and random manner. The response to repeated application of 5-HT was obtained in separate segments. RESULTS: Twenty-five segments from seven different coronary arteries were studied. Concentration-effect curves were fitted to the data using nonlinear regression analysis. The maximum contraction for L-775,606 was significantly less than that for sumatriptan with Emax values (% relative to 45 mm KCl=100%) of 30.1+/-4.22 and 41.5+/-2.7, respectively. L-775,606 was significantly (30-fold) less potent than sumatriptan in causing contraction compared with sumatriptan (EC50 values were 6.0 microm and 0.2 microm, respectively). For comparison the Emax value for 5-HT was 77.2% and the EC50 value was 0.2 microm. CONCLUSIONS: The selective 5-HT1D-receptor agonist L-775,606 has less propensity towards vasoconstriction in human isolated coronary artery (endothelium-denuded) than was mixed 5-HT1B/1D-receptor agonist sumatriptan. The contractions produced were at concentrations where L-775,606 would be expected to occupy 5-HT1B-receptors.

Adult↗
PubMed1999

Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine.

This multicentre, randomized, double-blind, placebo-controlled, parallel group dose-ranging study compared the efficacy and tolerability of four doses of sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute treatment of a single migraine attack. In total, 544 patients received the study medication as a single spray in one nostril, to treat a single migraine attack in the clinic. Efficacy assessments included the measurement of headache severity, clinical disability, and the presence/absence of associated symptoms. The incidence of headache recurrence was also assessed. The three highest doses of sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the placebo (25%) at providing headache relief (moderate or severe headache improving to mild or none) 120 min after treatment (P </= 0. 01). Also, the 20 mg dose was significantly superior to both the 10 and 5 mg doses at this time point (P < 0.05). The proportion of patients who were headache-free 120 min after treatment, was also higher following 20 mg (42%) rather than following any other sumatriptan dose (14-24%, P < 0.005 20 vs 10 mg) or placebo (11%). Headache recurrence in patients who had responded to initial treatment was reported by 30-41% of patients who received sumatriptan, compared with 33% of patients in the placebo group. Sumatriptan nasal spray was well tolerated, the incidence of adverse events with each dose of sumatriptan being similar to the placebo (20-27 and 23%, respectively). Apart from bad/bitter taste, the events were comparable with those reported following sumatriptan treatment by other routes of administration.

Adult↗
PubMed1993

Sumatriptan for the treatment of migraine attacks--a review of controlled clinical trials.

Sumatriptan, a 5HT1-like receptor agonist, is a completely new treatment principle for migraine. In an extensive international programme of controlled clinical trials, sumatriptan, 6 mg subcutaneously and 100 mg orally, was superior to placebo in reducing headache and associated symptoms. The response rate for subcutaneous sumatriptan (70-84% after 1 h and 81-87% after 2 h) was higher than for oral sumatriptan (50-67% after 2 h). Additional doses did not increase efficacy. Oral sumatriptan was superior to Cafergot (2 mg ergotamine plus 200 mg caffeine) and somewhat better than aspirin (900 mg) plus metoclopramide (10 mg). Recurrence of migraine occurred in approximately 40% of attacks. Side effects were generally mild and short-lived in the controlled clinical trials. However, in clinical practice sumatriptan has subsequently caused rare cases of heart ischemia and sumatriptan is contraindicated in patients with a history of ischemic heart disease.

Humans↗
PubMed1993

Sumatriptan relaxes isolated porcine ophthalmic artery, but inhibits VIP-induced relaxation.

Sumatriptan, a 5-hydroxytryptamine (5HT)1-like receptor agonist, is a new antimigraine drug which is also effective in cluster headache (CH), a disorder with marked ocular circulatory abnormalities. Sumatriptan could putatively exert a therapeutic effect in this vascular bed. The present study is an attempt to assess sumatriptan's vasoactivity in isolated porcine ophthalmic artery (POA) and to verify whether it has similar activity to 5HT, and whether it interferes with the vasodilation induced by calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP). In contrast to 5HT, sumatriptan induced only slight contraction in POA at high concentrations. However, in some artery segments pre-contracted with PGF2 alpha, sumatriptan induced a slight and short-lasting but marked relaxation. In addition, relaxations induced by VIP were inhibited significantly by sumatriptan, whereas CGRP effects were not influenced by the drug. Such reactions suggest that sumatriptan's effect in CH is probably unrelated to direct ocular arterial vasoconstriction.

Animals↗
PubMed1993

Amplifying effect of sumatriptan on noradrenaline venoconstriction in migraine patients.

The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxytryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 microgram dose, comparable to that induced by 0.5-1 micrograms of 5HT. This venoconstriction was completely inhibited by low doses of ketanserin (5 micrograms). Subcutaneous sumatriptan (6 mg) provoked a minor increase in vein tone, lasting less than 30 min. Non-venoconstrictive doses of sumatriptan (10-100 micrograms), injected in the hand vein, produced an amplification of NA-venoconstriction but not of 5HT-induced venoconstriction. A similar increased effect was displayed by subcutaneous sumatriptan (6 mg) for at least 1 h. Sumatriptan appears to cause peripheral venoconstriction only at high doses locally applied (in the hand vein), by acting on 5HT2 receptors. Clinical subcutaneous doses (6 mg) do not show significant venoconstrictive effects. The amplifying effect on NA venoconstriction, also caused by 5HT, ergotamine and dihydroergotamine in human cranial arteries, may be important in explaining the therapeutic action of sumatriptan in migraine attacks.

Adolescent↗
PubMed1996

Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem human brain.

The anatomical distribution of [3H]sumatriptan-binding sites was analysed in brain tissue sections from 11 subjects. Relevant concentrations of [3H]sumatriptan-binding sites were seen in areas such as visual cortex > locus niger > globus pallidus > layers IV-V of the frontal cortex > subiculum > entorhinal cortex > nucleus tractus solitarius > nucleus trigeminalis caudalis. This distribution of [3H]sumatriptan-binding sites in the human brain shows some differences when compared with that of 5HT1D receptors, confirming that, besides 5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences are evident between the distribution of [3H]sumatriptan-binding sites in the human brain and that reported for guinea-pig and rat brains, emphasizing that caution is needed in extrapolating experimental data from animals to humans. Furthermore, these data help to explain some of the therapeutic actions of sumatriptan. The remarkable levels of binding found in areas as nucleus tractus solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks sumatriptan could exert its specific anti-emetic effects and, partly at least, induce analgesia by directly acting over these brain nuclei.

Adult↗
PubMed1998

Consistency of response to sumatriptan nasal spray across patient subgroups and migraine types.

With an onset of headache relief as early as 15 min postdose compared with placebo, sumatriptan nasal spray is an important treatment option for patients who seek rapid headache relief and/or a convenient dosing form, whose migraine-associated nausea and vomiting render the use of an oral medication impractical, and those who prefer not to use an injectable form of migraine medication. Although the efficacy and tolerability of sumatriptan nasal spray are documented, the consistency of response to sumatriptan nasal spray across patient subgroups and migraine subtypes of importance to the prescribing clinician have not been described. To provide this information, data from four randomized, double-blind, parallel-group, placebo-controlled, multicenter studies (Glaxo Wellcome protocol numbers S2B-340, S2B-341, S2B-342, and S2B-T50), conducted between January 1993 and December 1994, were pooled and retrospectively analyzed to determine whether the efficacy and tolerability of sumatriptan nasal spray vary with gender, ethnic origin, age, weight, migraine type, concomitant or prior medication use, or pretreatment headache duration. Two-thousand-three-hundred-and-ninety-five (2395) patients treated a moderate or severe migraine with study medication in the four studies. The results demonstrate that sumatriptan nasal spray 20 mg and 10 mg were effective and well tolerated in the acute treatment of migraine consistently across a variety of patient and migraine subgroups. No clinically significant differences in headache relief or adverse event rates were observed for any of the subgroups examined. Approximately two-thirds of patients treated with sumatriptan nasal spray 20 mg compared with approximately one-third of placebo-treated patients reported headache relief 2 h postdose regardless of patient or migraine subgroup. The relationship between active treatment and placebo with respect to the overall incidence of adverse events also did not differ between patient or migraine subgroups. There is no evidence based on this analysis that sumatriptan nasal spray dosage should be adjusted in any of the subgroups examined.

Administration, Intranasal↗
PubMed1999

Sumatriptan nasal spray in the acute treatment of migraine: a review of clinical studies.

Sumatriptan nasal spray is a single-dose device that delivers 5 mg, 10 mg, or 20 mg of sumatriptan (dosage availability dependent upon country) in a 0.1 ml aqueous solution to one nostril. The efficacy and tolerability of sumatriptan nasal spray have been assessed in a number of studies. It has been demonstrated that administering sumatriptan as a divided dose in both nostrils confers no advantage over administration in a single nostril. It appears from these studies that sumatriptan nasal spray is rapidly effective (with an onset of efficacy as early as 15 min postdose). The 20 mg dose is superior to the lower doses (5 mg, 10 mg) in terms of both time to onset of efficacy and the extent of migraine symptom relief. Sumatriptan nasal spray is consistently effective in the treatment of multiple migraine attacks (with 67% of patients treated with the 20 mg dose responding in at least two of three treated attacks) and with long-term use for up to 1 year. Apart from a bitter taste, the adverse event profile of sumatriptan nasal spray is comparable to that of placebo.

Administration, Inhalation↗
PubMed2002

Characterization of sumatriptan-induced contractions in human isolated blood vessels using selective 5-HT(1B) and 5-HT(1D) receptor antagonists and in situ hybridization.

The 5-HT(1B/1D) receptor agonist sumatriptan is effective in aborting acute attacks of migraine and is known to cause constriction of cranial arteries as well as some peripheral blood vessels. The present study set out to investigate whether 5-HT(1B) and/or 5-HT(1D) receptors mediate contractions of the human isolated middle meningeal and temporal arteries (models for anti-migraine efficacy) and coronary artery and saphenous vein (models for side-effect potential). Concentration-response curves were made with sumatriptan (1 nm-100 microm) in blood vessels in the absence or presence of selective antagonists at 5-HT(1B) (SB224289) and 5-HT(1D) (BRL15572) receptors. SB224289 antagonized sumatriptan-induced contractions in all blood vessels, although the antagonism profile was different amongst these blood vessels. In the temporal artery, SB224289 abolished contraction to sumatriptan, whereas in the middle meningeal artery and saphenous vein sumatriptan-induced contractions were blocked in an insurmountable fashion. Moreover, SB224289 acted as a weak surmountable antagonist in the coronary artery (pK(B): 6.4 +/- 0.2). In contrast, BRL15572 had little or no effect on sumatriptan-induced contractions in the four blood vessels investigated. In situ hybridization revealed the expression of 5-HT(1B) receptor mRNA in the smooth muscle as well as endothelial cells of the blood vessels, whereas the mRNA for the 5-HT(1D) receptor was only very weakly expressed. These results show that the 5-HT(1B) receptor is primarily involved in sumatriptan-induced contractions of human cranial as well as peripheral blood vessels.

Adult↗
PubMed2002

CNS effects of sumatriptan and rizatriptan in healthy female volunteers.

This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9) degrees/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8) degrees/sec). Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). Temazepam caused larger, similar effects. In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation.

Adult↗
PubMed1998

Chronic paroxysmal hemicrania and hemicrania continua: lack of efficacy of sumatriptan.

Attacks of chronic paroxysmal hemicrania are prevented by the continuous administration of indomethacin. Sumatriptan, an agonist of 5-HT1-like receptors, has proven effective in the treatment of cluster headache attacks. There are clear clinical similarities between chronic paroxysmal hemicrania and cluster headache. A natural consequence of these considerations would be to establish whether chronic paroxysmal hemicrania also responds similarly to sumatriptan. Since hemicrania continua is another unilateral headache responsive to indomethacin, it would be meaningful to also include hemicrania continua in such a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7 patients (6 women and 1 man) with chronic paroxysmal hemicrania and 7 patients (5 women and 2 men) with hemicrania continua. In chronic paroxysmal hemicrania, the mean interval between the last three attacks prior to sumatriptan treatment (40 +/- 23 minutes) was not statistically different from the mean interval between the three attacks subsequent to sumatriptan treatment of an attack (32 +/- 20 minutes). In none of the patients did the mean duration of the "test attack" decrease as compared to the attacks antedating the test attack (25 +/- 11 minutes and 19 +/- 9 minutes, respectively) (P = 0.027, Wilcoxon). In 2 patients with chronic paroxysmal hemicrania, placebo (saline) administration did not lead to any change in the interval between attacks. There was a mild, but statistically significant reduction in visual analog scale values for headache intensity in hemicrania continua (P = 0.04, Wilcoxon). There was no clear, i.e., clinically meaningful, reduction in visual analog scale values in any particular patient with hemicrania continua. Taken together, these results seem to show that sumatriptan is of no benefit in chronic paroxysmal hemicrania, but may have a partial efficacy in hemicrania continua. However, the latter effect is clinically unimportant. This minor difference in regard to the clinical effect may, nevertheless, be of some interest pathogenetically, indicating minor differences between the two headaches. The lack of sumatriptan effect in chronic paroxysmal hemicrania clearly and markedly strengthens the nonalignment concept in regard to chronic paroxysmal hemicrania and cluster headache.

Adult↗
PubMedDate not supplied

Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group.

Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.

Administration, Oral↗
PubMedDate not supplied

Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan.

OBJECTIVES: To determine whether 347 patients would respond to a 50-mg oral dose of sumatriptan, even though they considered themselves poor responders to this acute therapy for migraine, and to investigate whether oral naratriptan can be an effective acute therapy for migraine in the subset of patients who did not respond to sumatriptan under double-blind, well-controlled conditions. BACKGROUND: Although most migraineurs respond to sumatriptan, there remains a need for an effective alternative for those who do not respond. Naratriptan is a more potent and more lipophilic member of this class of agent and could prove beneficial in such patients. This is the first well-controlled study to assess the value of another 5-HT1B/1D agonist in this difficult patient subset. METHODS: This study comprised two migraine attacks. The first (attack 1) was a single-blind assessment of the efficacy of sumatriptan (50 mg orally) in patients with a history of poor response to the drug. The second (attack 2) was a randomized, parallel group, double-blind, placebo-controlled trial of naratriptan (2.5 mg orally) in nonresponders to oral sumatriptan. RESULTS: Attack 1: About two thirds of this selected migraine population did not respond to sumatriptan. Attack 2: Naratriptan was statistically superior to placebo for headache relief at 2 hours and 4 hours, as well as for most other features of migraine attacks. These data suggest an intrinsic efficacy of naratriptan in this patient subset and not a coincidental response. No unexpected tolerability issues arose. CONCLUSIONS: Naratriptan is an alternative therapy for migraineurs who respond poorly to oral sumatriptan. No response to one "triptan" does not necessarily predict no response to them all.

Administration, Oral↗
PubMedDate not supplied

2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study.

BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.

Administration, Oral↗
PubMed2001

Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.

OBJECTIVE: To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild-to-moderate migraine, with or without aura, when taken at the first sign of an attack. BACKGROUND: The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment. METHODS: This was a multicenter, double-blind, randomized, parallel-group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled. RESULTS: One hundred thirty-seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24-hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group. CONCLUSIONS: Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.

Acetaminophen↗