sumatriptan, Imitrex
Sumatriptan in clinical practice: a 2-year review of 453 migraine patients.

Visser WH, de Vriend RH, Jaspers MW, Ferrari MD.

Department of Neurology, University Hospital, Leiden, The Netherlands.

The long-term and within-patient consistency of the efficacy and tolerability of subcutaneous and oral sumatriptan in migraine was studied by retrospective survey of 2 years with mailed self-administered questionnaires in our neurology outpatient clinic. Subjects were migraine patients with or without aura (N = 869). We measured long-term use of sumatriptan and within-patient consistency and change over time of headache relief, headache recurrence, and chest symptoms after sumatriptan. The questionnaire was returned by 735 (85%) patients; 453 had used sumatriptan for nearly 28,000 attacks during 25 (median) months (92% > 1 year). Sumatriptan provided headache relief, mostly within 2 hours, in 85% of patients in at least two-thirds of their attacks. Of all patients, 75% experienced (usually multiple) headache recurrences in at least some and 40% in (nearly) all attacks. Median time to recurrence was 8 to 12 hours (range 1 to 30). Recurrence of aura was reported as well. Over 2 years, efficacy of sumatriptan had waned in 18% of patients (mainly because of increase in headache recurrence) and improved in 12% (mainly because of reduction of headache recurrence or adverse events or increase of headache relief); the number of monthly doses of sumatriptan had increased in 20%, reduced in 35%, and not changed in 45% of patients. Chest symptoms occurred in up to 58% of patients in at least some and in up to 42% of patients in all attacks, causing discontinuation of sumatriptan in 10%. In total, 111 patients (25%) discontinued sumatriptan mainly because of headache recurrence, adverse events, insufficient headache relief, or high price. In most patients, the effects of sumatriptan were consistent within subjects and over time. In most patients, sumatriptan provided rapid headache relief. Multiple headache recurrence was the major limitation. Chest symptoms were frequent but usually not serious if patients were forewarned.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8710123&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
[3H]Sumatriptan binding sites in human brain: regional-dependent labelling of 5-HT1D and 5-HT1F receptors.

Pascual J, Del Arco C, Romon T, Del Olmo E, Pazos A.

Department of Physiology and Pharmacology, University of Cantabria, Santander, Spain.

The general properties of [3H]sumatriptan binding sites in postmortem human brain tissue sections are described. High concentrations of autoradiographic grains were seen in globus pallidus = substantia nigra > cortex > putamen > hippocampus. While 5-HT (5-hydroxytryptamine) displaced in all regions more than 90% of [3H]sumatriptan binding, the level of binding inhibited by 5-CT (5-carboxamidotryptamine) varied in each region. Although the binding inhibited by 5-CT in some regions such as globus pallidus and substantia nigra was equivalent to that obtained with 5-HT, in cortical areas, such as frontal cortex and hippocampus, a substantial level of binding insensitive to 5-CT was seen. In addition, in membrane binding assays, 10 nM metergoline displaced most [3H]sumatriptan specific binding in striatum and only 16% in frontal cortex. In the human brain sumatriptan binds to at least two 5-HT1 receptors, 5-HT1D and 5-HT1F.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8720594&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Blockade of porcine carotid vascular response to sumatriptan by GR 127935, a selective 5-HT1D receptor antagonist.

De Vries P, Heiligers JP, Villalon CM, Saxena PR.

Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.

1. It has previously been shown that the antimigraine drug, sumatriptan, a putative 5-HT1D receptor agonist, decreases porcine common carotid and arteriovenous anastomotic blood flows, but slightly increases the arteriolar (capillary) blood flow to the skin and ears. Interestingly, such responses, being mediated by 5-HT1-like receptors, are resistant to blockade by metergoline, which, in addition to displaying a very high affinity for (and occasionally intrinsic efficacy at) the 5-HT1D receptor subtypes, blocks (with lower potency than methiothepin) some 5-HT1D receptor-mediated vascular responses. These findings raise doubts whether sumatriptan-sensitive 5-HT1-like receptors mediating changes in the distribution of porcine carotid blood flow are identical to cloned 5-HT1D receptors. With the recent advent of the potent and selective 5-HT1D receptor antagonist, GR127935, we have examined in the present study whether the carotid vascular effects of sumatriptan in the pig are amenable to blockade by GR127935. 2. In animals pretreated with saline, sumatriptan (30, 100 and 300 micrograms kg-1, i.v.) reduced the total carotid and arteriovenous anastomotic blood flows in a dose dependent manner. In contrast, sumatriptan increased blood flow to the skin, ears and fat, although the total capillary fraction was not significantly affected. 3. While GR127935 pretreatment (0.25 and 0.5 mg kg-1) itself slightly reduced the total carotid and arteriovenous anastomotic blood flows, carotid vasoconstrictor responses to sumatriptan were either partly (0.25 mg kg-1) or completely (0.5 mg kg-1) blocked by the compound. In GR127935 pretreated animals, the sumatriptan-induced increases in blood flow to the skin, ears and fat were also attenuated. 4. Taken together, the results suggest that arteriovenous anastomotic constriction and, possibly, arteriolar dilatation in the skin, ears and fat by sumatriptan are mediated by 5-HT1D receptors. Therefore, vascular 5-HT1-like receptors in the porcine carotid bed appear to be identical to 5-HT1D receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8733580&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Is overuse of sumatriptan a problem? A population-based study.

Gaist D, Hallas J, Sindrup SH, Gram LF.

Department of Clinical Pharmacology, IMB, Odense University, Denmark.

OBJECTIVE: Sumatriptan is highly efficacious in aborting acute attacks of migraine. Owing to recent reports of misuse of sumatriptan, we performed a study of its use in a Danish population. METHODS: Data were retrieved from a prescription database covering a period of 27 months after release of the drug. Consumption was described by the defined daily dose (DDD) unit and total individual consumption during the period was calculated. Those who received more than one prescription for sumatriptan were classified according to peak use of sumatriptan into high (> or = 60 DDD/31 days) (n = 45), intermediate (30-59 DDD/31 days) (n = 127) and low (< 30 DDD/31 days) (n = 1423) consumption groups. Individual usage of other medication was described. RESULTS: We identified 2,878 users of sumatriptan, of whom 1,283 (45%) only redeemed one prescription. The use of sumatriptan was highly skewed. The 1% heaviest users accounted for 20% of the total consumption. The median total individual consumption of sumatriptan was 500 DDD, 192 DDD, and 24 DDD in the three groups of multiple redeemers, respectively. Pronounced differences in the total amounts of opioids and ergot alkaloids used were also found, with the high peak consumption group being the heaviest consumers of all drug categories, although half of them had only received large doses of sumatriptan. Fifty seven % of high peak users redeemed more than 29 DDD of sumatriptan within one month of initiation of treatment. The 45 high peak users had received the bulk of their medication, largely in tablet formulation, from 31 prescribers. The data points to rebound headache as a plausible underlying mechanism, but incorrect use of sumatriptan for migraine prophylaxis is also a possibility. Overuse of sumatriptan has serious economic consequences and its long-term health effects are not known.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8737753&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
EEG and topographic frequency analysis in migraine attack before and after sumatriptan infusion.

Thomaides T, Tagaris G, Karageorgiou C.

Neurology Department, General Hospital of Athens, Greece.

Electroencephalographic changes occurring in patients with migraine have received much attention. Although in migraineurs a number of studies have been done after nitroglycerin-induced attacks, there is no reported EEG study before and after nitroglycerin-induced sumatriptan-treated attacks. We, therefore, studied the EEG topographic frequency analysis in 19 symptom-free, otherwise healthy, unmedicated patients with common migraine and in 19 age- and sex-matched controls before nitroglycerin, at the time of maximum pain, and 30 minutes after sumatriptan. During headache attacks, an increase of slow rhythmic activity of the theta and delta range and a decrease of activity in the alpha and beta range were observed. These abnormalities disappeared 30 minutes after a sumatriptan injection. This suggests that common migraine is associated with disturbances of cortical electrogenesis and may provide insight into the causes of migraine and aid in the development of effective therapies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8742685&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Dual effect of the serotonin agonist, sumatriptan, on peripheral neurogenic inflammation.

Pierce PA, Xie GX, Peroutka SJ, Levine JD.

Department of Anesthesia, University of San Francisco, California 94143-0648, USA.

BACKGROUND AND OBJECTIVES. Sumatriptan is a novel drug for migraine headache pain, which, on the basis of its mechanism of action, may have therapeutic potential in other pain states. Sumatriptan inhibits neurogenic inflammation in dural vessels by activating the 5-HTIB and 5-HTID inhibitory serotonin (5-hydroxytryptamine [5-HT]) receptor subtypes on terminals of trigeminal neurons. This study was designed to determine the role of sumatriptan in peripheral pain mechanisms by detecting whether 5-HTIB and 5-HTID receptors and the recently cloned excitatory 5-HT7 receptor, for which sumatriptan displays moderate binding affinity, are present in peripheral sensory neurons, and by determining the effect of sumatriptan on peripheral neurogenic inflammation. METHODS. A polymerase chain reaction (PCR) technique was used to detect mRNA for 5-HT receptors in rat lumbar dorsal root ganglia. Rat knee joint plasma extravasation was used to determine the effect of sumatriptan on peripheral neurogenic inflammation. RESULTS. The mRNA for the sumatriptan-activated receptors 5-HTIB, 5-HTID, and 5-HT7, was detected in lumbar dorsal root ganglia. In rat knee joint, capsaicin-activated C-fibers stimulated plasma extravasation to 273 +/- 62% of baseline. Low-concentration sumatriptan (50 nM) significantly inhibited capsaicin-induced plasma extravasation to 106 +/- 6% of baseline. High-concentration sumatriptan (1 microM) significantly enhanced capsaicin-induced plasma extravasation to 572 +/- 55% of baseline. CONCLUSIONS. Sumatriptan inhibits peripheral neurogenic inflammation, probably via 5-HT1B/1D receptors, and may be a novel therapy for inflammatory pain states. However, high concentrations (> 200 nM) may enhance neurogenic inflammation, possibly by activation of 5-HT7 receptors, which may explain lack of migraine relief and excessive injection site pain in 20-30% of patients treated with sumatriptan.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8744664&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
How does sumatriptan perform in clinical practice?

Dahlof CG.

Gothenburg Migraine Clinic, Sweden.

The patient's opinion on sumatriptan treatment has been obtained from 351 migraineurs (299F and 52M) by means of a telephone survey. The results are based on the patient's cumulative experience of more than 20,000 subcutaneous injections and more than 2,000 tablet doses. The average period during which subcutaneous sumatriptan (12 mg/ml, 0.5 ml) was used was 19.1 +/- 0.4 months and 84% of the patients had used more than 10 injections. The average number of migraine attacks per month was 3.0 +/- 0.1, injections per attack 1.7 +/- 0.1, and number of tablets (100 mg) per attack 1.8 +/- 0.2. Attack duration was decreased from on average 38.4 +/- 2.1 h to 2.3 +/- 0.5 h by subcutaneous sumatriptan and to 3.4 +/- 1.0 by orally administered sumatriptan. The average degree of efficiency at work with migraine was 76.3 +/- 1.9% on sumatriptan compared with 26.6% on other treatment options; 85% said that sumatriptan was much better than previous conventional therapies tested. During their experience with sumatriptan, 89% of the migraineurs reported altogether 1,058 adverse events (average 3.6 +/- 01, range 1 to 12) in connection with subcutaneous sumatriptan treatment. The three most frequent were drowsiness/sedation (49%), chest symptoms (40%) and injection site symptoms (37%). Among the table users, 87% reported altogether 122 adverse events (average 2.6 +/- 0.3, range 1 to 11). Seventy-eight percent of the responders responded to subcutaneous sumatriptan sometimes (22% always, 15% every second attack, 40% seldom) experienced a recurrence of their headache within 24 h. The average number of recurrences was 1.7 +/- 0.1 and the average time to recurrence 13.0 +/- 0.6 h (range 1.5-24 h). It is concluded that the selected group of migraineurs found sumatriptan to be very effective in reducing the symptoms of their migraine attacks, but also to cause several adverse events, in many cases, with short-lasting effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8749242&dopt=Abstract sumatriptan Imitrex