sumatriptan, Imitrex
Decision making in migraine patients taking sumatriptan: an exploratory study.

Ivers H, McGrath PJ, Purdy RA, Hennigar AW, Campbell MA.

School of Psychology, Laval University, Quebec City, Quebec, Canada.

Until recently, much of the medical and psychological literature has examined and conceptualized the taking of medication from the viewpoint of adherence to or compliance with recommendations from health professionals. However, some authors have argued that medication taking is mostly determined by patient decision making. In order to investigate the factors and processes influencing the patient's decision to take or not take abortive therapy for migraines, 20 migraineurs (according to International Headache Society criteria) were asked, using a semistandardized interview, what factors influenced their decision to take or not take sumatriptan when they had a migraine. Qualitative analysis revealed a 2-stage decision-making process. First, the patient collects information from interoceptive and environmental cues (symptom monitoring) to predict whether the headache that is beginning will become a migraine. Then, if the patient decides it is a migraine, he or she weighs various factors to decide whether to take sumatriptan. These results are consistent with the current cognitive psychology literature on decision-making processes and could lead to significant improvements in understanding the process by which patients make decisions about taking sumatriptan and, ultimately, could lead to better patient education and more effective headache control. They also open a whole new field in the empirical investigation of medication-taking behavior.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10759912&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Permeation of sumatriptan through human vaginal and buccal mucosa.

van der Bijl P, Penkler L, van Eyk AD.

Oral and Dental Research Institute, Faculty of Dentistry, University of Stellenbosch, Tygerberg, South Africa.

Continued interest in the various routes by which sumatriptan may be administered prompted us to investigate its passage through buccal mucosa. Because human buccal mucosa is scarce, we proposed using the relatively abundant vaginal mucosa, which has been shown to have comparable diffusion rates for a number of widely varying molecules, as a model of buccal mucosa. In addition, by comparing these two tissues with respect to their permeability to sumatriptan, the human vaginal/buccal mucosa model could be further evaluated. Clinically healthy human vaginal and buccal mucosa specimens were used in the permeability studies. Permeability to sumatriptan was determined using a continuous flow-through diffusion system in the presence and absence of permeation enhancers. No statistically significant differences in permeability could be demonstrated for both mucosae toward sumatriptan. Flux values obtained in the absence and presence of glycodeoxycholate and lauric acid (1:1 molar ratio) to sumatriptan of buccal and vaginal mucosa, respectively, were not significantly different. The results obtained further support the hypothesis of the vaginal/buccal mucosal in vitro permeability model and suggest that this model may be used in conjunction with various absorption enhancers. Further studies on the buccal route of absorption of sumatriptan are thus warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10759913&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Diffusion-weighted MRI used to detect in vivo modulation of cortical spreading depression: comparison of sumatriptan and tonabersat.

Bradley DP, Smith MI, Netsiri C, Smith JM, Bockhorst KH, Hall LD, Huang CL, Leslie RA, Parsons AA, James MF.

Herchel Smith Laboratory for Medicinal Chemistry, University of Cambridge, Robinson Way, Cambridge CB2 2PZ, United Kingdom.

Spreading cortical depolarization and depression of electroencephalographic activity (SD) may underlie the aura and spreading neurovascular events of migraine. Cortical depolarization may also precipitate the progressive development of cerebral pathology following ischemia. However, data on SD in the human brain are sparse, most likely reflecting the technical difficulties involved in performing such clinical studies. We have previously shown that the transient cerebral water disturbances during SD can be quantitatively investigated in the gyrencephalic brain using repetitive diffusion-weighted magnetic resonance imaging (DWI). To investigate whether DWI could detect modulation of the spatiotemporal properties of SD in vivo, the effects of the antimigraine drug sumatriptan (0.3 mg/kg iv) and the novel anticonvulsant tonabersat (10 mg/kg ip) were evaluated in the cat brain. Supporting previous findings, sumatriptan did not affect the numbers of events (range, 4-8), the duration of SD activity (39.8 +/- 4.4 min, mean +/- SEM), and event velocity (2.2 +/- 0.4 mm min(-1)); tonabersat significantly reduced SD event initiation (range, 0-3) and duration (13.2 +/- 5.0 min) and increased primary event velocity (5.4 +/- 0.7 mm min(-1)). However, both drugs significantly decreased, by >50%, the spatial extent of the first KCl-evoked SD event, and sumatriptan significantly increased event propagation across the suprasylvian sulcus (5.5 +/- 0.6 vs 2.4 +/- 0.4 events in controls). These results demonstrate (1) the feasibility of using DWI to evaluate therapeutic effects on SD, and (2) that sumatriptan may directly modulate the spatial distribution of SD activity in the gyrencephalic brain. (c)2001 Elsevier Science.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11716558&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Monitoring birth outcomes in the Sumatriptan Pregnancy Registry.

Eldridge RR, Ephross SA.

Glaxo Wellcome, Research Triangle Park, North Carolina, USA

Background: Health professionals often need to make medical management decisions by weighing potential risk versus benefit. Because 50% of pregnancies in the United States are unplanned, the likelihood for unintentional first-trimester exposure to medications is high and increases when women of childbearing potential (ages 15-44) are taking medications used to treat chronic or recurrent conditions, such as migraine. Prospective collection of pregnancy exposure and outcome data is one method for providing data to the medical community as a tool for making risk assessments.Methods: The Sumatriptan Pregnancy Registry is an international, exposure-registration and follow-up study to prospectively collect prenatal sumatriptan exposure and outcome data. An advisory committee reviews data and assists in disseminating information. Committee members include independent scientists with expertise in obstetrics, pediatrics, neurology, internal medicine, epidemiology, clinical genetics, and teratology.Results: As of April 30, 1997, 181 outcomes were prospectively reported from pregnancies involving use of sumatriptan. Of the 171 outcomes where earliest exposure was in the first trimester there were 143 infants without birth defects, 4 live infants with birth defects, 1 stillbirth with birth defects [12 spontaneous pregnancy losses, 2 stillbirths, and 9 induced abortions without birth defects]. The proportion of outcomes involving birth defects, 5/148, 3.4% (95% CI 1.3%, 8.1%), does not differ from the expected proportion in the general population.Conclusions: To date, no pattern has emerged in either the prospectively or retrospectively reported defects. Registry data are disseminated to interested health care providers who are then in a more informed position when making medical management decisions. However, more data are needed before definitive conclusions can be drawn about the safety of sumatriptan use in pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10838359&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Zolmitriptan: new product. Similar to sumatriptan.

[No authors listed]

(1) Zolmitriptan is an antimigraine drug similar to sumatriptan. (2) The clinical file mainly comprises placebo-controlled dose-finding studies recommending an optimal oral dose of 2.5 mg. (3) Zolmitriptan has been compared with sumatriptan in a trial that showed no difference in efficacy. In particular, the recurrence rate of headache after initial relief was not lower on zolmitriptan than on sumatriptan. (4) The safety profile of zolmitriptan is similar to that of sumatriptan. The contraindications relating to a history of cardiovascular disease must be respected because of the vasoconstrictive effect of the drug. (5) Zolmitriptan has the same drug interactions as sumatriptan. Moreover, zolmitriptan should not be used during migraine attacks by patients on propranolol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10848058&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
The in vivo pharmacological profile of eletriptan (UK-116,044): a potent and novel 5-HT(1B/1D) receptor agonist.

Gupta P, Butler P, Shepperson NB, McHarg A.

Department of Discovery Biology, Pfizer Central Research, Sandwich, CT13 9NJ, Kent, UK.

The anti-migraine drug, eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1 H-indole; UK-116,044], is a novel 5-HT(1B/1D) receptor agonist. In this paper, the regional vasoconstrictor profile of eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibitory actions of eletriptan on neurogenic inflammation in rat dura mater were also assessed. In the anaesthetised dog, eletriptan (1-1000 microg kg(-1) i.v.) produced a dose-dependent reduction of carotid arterial blood flow with a similar potency and maximum effect to sumatriptan (ED(50) values: eletriptan and sumatriptan, 12 and 9 microg kg(-1), i.v., respectively). However, eletriptan exhibited a significantly lower potency than sumatriptan in reducing coronary artery diameter (ED(50) values: 63 and 19 microg kg(-1), i.v., respectively, P<0.05). In the femoral circulation, sumatriptan caused a significant reduction in arterial blood flow (ED(50) 35 microg kg(-1) i.v.) whereas eletriptan (1-1000 microg kg(-1) i.v.) had no significant effect upon femoral arterial blood flow when compared to vehicle-treated animals. In rats, eletriptan (30-300 microg kg(-1) i.v.) administered prior to electrical stimulation of the trigeminal ganglion produced a dose-related and complete inhibition of plasma protein extravasation in the dura mater (mean extravasation ratio: control 1.9; eletriptan 1.0, minimum effective dose 100 microg kg(-1), P<0.05). The potency and maximum effect of eletriptan was identical to that of sumatriptan in this model. When administered during a period of continual stimulation of the trigeminal nerve, eletriptan (100 microg kg(-1) i.v.) produced a complete inhibition of plasma protein extravasation. The ability to reduce canine carotid arterial blood flow and inhibit neurogenic inflammation in rat dura mater suggests that vascular and neurogenic mechanisms may contribute to eletriptan's clinical efficacy in migraine patients. In addition, eletriptan exhibits some selectivity for reducing carotid arterial blood flow when compared with femoral arterial blood flow and coronary artery diameter, in the anaesthetised dog.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10856450&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Sumatriptan modifies cortical free radical release during cortical spreading depression. A novel antimigraine action for sumatriptan?

Read SJ, Parsons AA.

Neuroscience Research, SmithKline Beecham Pharmaceuticals, Third Avenue, Harlow, CM19 5AW, Essex, UK.

Increases in concentration of brain NO are proposed to initiate and mediate migraine headache. Triggered by focal depolarisation, spreading depression (SD) represents a suitable mechanism for eliciting widespread release of nitric oxide. The current study examines the effect of sumatriptan, a 5-HT(1B/1D) agonist and effective antimigraine therapy, on free radical release (nitric oxide and superoxide) in SD in the simple and complex cortices of the rat and cat. Following initiation of SD, sumatriptan pretreatment (300 microg kg(-1) i.v., 15 min prior to SD) modulated all phases of nitric oxide release associated with each SD in both cats and rats. As a result, superoxide levels were observed to significantly (ANOVA, post hoc LSD) increase versus vehicle treated animals (saline 1 ml kg(-1) i.v. 15 min prior to SD) during specific phases of each SD depolarisation. Averaged over all SD depolarisations, mean peak SD nitric oxide levels per depolarisation were 0.73+/-0.23 microM (n=29) in cats, and 0.42+/-0.09 microM (n=34) in rats. Sumatriptan significantly (Students t-test, P<0.05, two tailed hypothesis, P<0.05) modulated this increase in cortical nitric oxide concentrations to 0.32+/-0.06 microM (n=25) and 0. 22+/-0.07 microM (n=37) in cats and rats. Sumatriptan appears to decrease the amplitude of nitric oxide release but enhances extracellular superoxide concentrations in both lissencephalic and gyrencephalic cortices during SD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10869500&dopt=Abstract sumatriptan Imitrex