sumatriptan, Imitrex
Are triptans with enhanced lipophilicity used for the acute treatment of migraine associated with an increased consulting rate for depressive illness?

Millson D, Frischer M, Croft P, Goadsby PJ.

Primary Care Sciences Research Centre, Keele University, London, UK. d.millson keele.ac.uk

1997, sumatriptan-treated migraineurs had significantly higher depression PCRs (22.3%) compared with non-triptan users (19.3%), a difference of 6.4% (95% confidence interval (CI) 4.6-8.4%, P < 0.001). In the year (April 1997 to March 1998) following the launch of the TELs, depression PCRs were significantly higher among patients using these compounds compared with sumatriptan-treated patients (5.1%, CI 1.8-12.0%, P < 0.05). However, after taking account of prior depression (odds ratio (OR) 6.45, 95% CI 3.63-11.43), TELs were not significantly associated with depression (OR 0.27, 95% CI 0.03-2.13). Furthermore, rates of newly diagnosed depression after treatment were similar in the two triptan groups (sumatriptan 4.2%; TELs 3.9%). Although, the TELs are being prescribed to patients with higher pre-existing rates of depression, they are not associated with subsequently increased consulting for depressive illness compared with patients taking sumatriptan. This study highlights the potential to use GPRD to test targeted hypotheses exploring pharmacovigilance issues for patients using new medicines.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11167903&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male rats.

Einer-Jensen N, Larsen L, Deprez S, Starns E, Schwartz S.

Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, Winsloewparken 21, DK-5000 Odense C, Denmark.

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. This model was used to investigate whether the antimigraine 5HT(1B/1D) receptor agonists sumatriptan and naratriptan may also be transferred by the system. The ratio of 'head':'heart' plasma concentrations obtained from two carotid catheters after intranasal administration was not different from 1.00 for either compound, and thus, there was no experimental evidence of a preferential local transfer of drug from the nose to the carotid artery circulation. However, plasma concentrations increased from the first minute after intranasal dosing suggesting that sumatriptan and naratriptan are absorbed into the general systemic circulation from the nasal cavity in rats in a first-order fashion with no lag time. This is consistent with the clinical onset of efficacy of sumatriptan after an intranasal dose which occurs as early as 15 min post dose. Copyright 2001 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11745923&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Unravelling the pharmacological profile of the canine external carotid vasodilator '5-HT1-like' receptors: coexistence of sympatho-inhibitory 5-HT1B and postjunctional 5-HT7 receptors.

Villalon CM, Sanchez-Lopez A, Centurion D, Saxena PR.

Departamento de Farmacobiologia, CINVESTAV-IPN, Mexico. carlos_villalon infosel.net.mx

It has been suggested that the external carotid vasodilatation produced by serotonin (5-hydroxytryptamine; 5-HT) in anaesthetised dogs with intact vagosympathetic trunks is mediated by sympatho-inhibitory '5-HT1D' receptors and musculotropic '5-HT1-like' receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors. In pentobarbital-anaesthetised dogs with intact vagosympathetic trunks, 1-min intracarotid (i.c.) infusions of 5-carboxamidotryptamine (5-CT; 0.01-0.3 microg/min), 5-HT (0.3-30 microg/ min), 5-methoxytryptamine (5-MeO-T; 1-100 microg/min) or sumatriptan (1-100 microg/min) dose-dependently increased the external carotid blood flow without affecting blood pressure or heart rate. The selective 5-HT1D receptor agonist, PNU-142633 (1-1000 microg/min), was essentially inactive. After mesulergine (300 microg/kg, i.v.), an antagonist at cardiovascular 5-HT7 receptors, the above responses to 5-HT, 5-CT and 5-MeO-T were blocked, whilst those to sumatriptan remained unaffected. In contrast, after the 5-HT1B/1D receptor antagonist, GR127935 (10 microg/kg, i.v.), the responses to 5-HT, 5-CT and 5-MeO-T were not affected, but those to sumatriptan were abolished. Furthermore, after the selective 5-HT1B receptor antagonist, SB224289 (300 microg/kg, i.v.), the responses to 5-HT, 5-CT and 5-MeO-T were significantly enhanced, whereas those to sumatriptan were abolished. Interestingly, the responses to all these agonists remained unmodified after the selective 5-HT1D receptor antagonist, BRL15572 (300 microg/kg, i.v.). The above results suggest that the '5-HT1-like' receptors, which mediate canine external carotid vasodilatation, display the pharmacological profile of sympatho-inhibitory 5-HT1B receptors and musculotropic 5-HT7 receptors, and confirm the existence of vasoconstrictor 5-HT1B receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11191839&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Pharmacology and efficacy of eletriptan for the treatment of migraine attacks.

Diener HC, McHarg A.

Department of Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.

Sumatriptan, a 5-HT 1B/1D agonist, was introduced 10 years ago and was the most effective therapy for migraine attacks at that time. Eletriptan is a new 5-HT 1B/1D agonist with high potency and selectivity at 5-HT 1B/1D receptors. It is effective in animal models in which the vascular and neurogenic mechanisms implicated in migraine were measured. Eletriptan is selective for the intracranial blood vessels over other extracranial vasculature, in particular coronary arteries. Eletriptan has a rapid and complete oral absorption and a good oral bioavailability in migraineurs. In comparative trials 20 mg, 40 mg and 80 mg eletriptan, 100 mg sumatritpan and placebo were compared for the treatment of migraine attacks. All three doses of eletriptan were statistically superior to placebo for headache response and headache-free patients. The 80 mg dose of eletriptan was also superior to sumatriptan 100 mg. Headache recurrence, defined as return of moderate or severe headache within 24 hours of dosing and following a headache response at two hours after initial dosing, occurred in 33% of the patients following 100 mg sumatriptan and in 28%, 34% and 32% after 20 mg, 40 mg and 80 mg eletriptan. In another large trial, headache response rates were significantly higher for both doses of eletriptan (64% for 40 mg and 67% for 80 mg) than for two doses of sumatriptan (50% for 50 mg and 53% for 100 mg). Eletriptan 40 mg or 80 mg was also superior to ergotamine plus caffeine (Cafergot). In summary, eletriptan is a highly effective and fast-acting drug for the treatment of acute migraine attacks.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11221281&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Comparative effects of frovatriptan and sumatriptan on coronary and internal carotid vascular haemodynamics in conscious dogs.

Carel I, Ghaleh B, Edouard A, Dubois-Rande JL, Parsons AA, Giudicelli JF, Berdeaux A.

Departement de Pharmacologie, Faculte de Medecine Paris Sud and INSERM E 00.01, 63 rue Gabriel Peri, 94276 Le Kremlin Bicetre Cedex, France.

The effects of frovatriptan and sumatriptan on internal carotid and coronary vascular haemodynamics were investigated and compared in conscious dogs. Frovatriptan and sumatriptan (0.1 - 100 microg kg(-1)) induced a transient increase in external coronary artery diameter (eCOD) of up to 2.9+/-1.2 and 1.8+/-0.6%, respectively (both P:<0.05). This was followed by a prolonged and dose-dependent decrease in eCOD of up to -5.2+/-1.2 and -5.3+/-0.9% (both P:<0.05), with ED(50) values of 86+/-21 and 489+/-113 micromol kg(-1), respectively. In contrast, only a decrease in the external diameter of the internal carotid artery was observed (-6.0+/-0.6 and -6.2+/-1.4%, both P:<0.05, and ED(50) values of 86+/-41 and 493+/-162 micromol kg(-1), respectively). Frovatriptan was thus 5.7 fold more potent than sumatriptan at the level of both large coronary and internal carotid arteries. After endothelium removal by balloon angioplasty in coronary arteries, the initial dilatation induced by the triptans was abolished and delayed constriction enhanced. The selective antagonist for the 5-HT(1B) receptors SB224289 dose-dependently blocked the effects of sumatriptan on large coronary and internal carotid arteries whereas the selective antagonist for the 5-HT(1D) receptors BRL15572 did not affect any of these effects. In conclusion, frovatriptan and sumatriptan initially dilate and subsequently constrict large coronary arteries in the conscious dog, whereas they directly constrict the internal carotid artery. The vascular endothelium modulates the effects of these triptans on large coronary arteries. Finally, 5-HT(1B) but not 5-HT(1D) receptors are primarily involved in canine coronary and internal carotid vasomotor responses to sumatriptan.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11226138&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Sumatriptan injection and tablets in clinical practice: results of a survey of 707 migraineurs.

Dahlof CG, Saiers J.

Goteborg Migraine Clinic, Sociala Huset, Uppg D II, S-411 17, Goteborg, Sweden.

This report from the Gothenburg Migraine Clinic in Sweden describes the results of a telephone survey of over 700 patients using open-label sumatriptan tablets or sumatriptan injection for the treatment of migraine. The information is based on the patients' cumulative experience of more than 76,000 subcutaneous injections, 56,000 tablets 100 mg, and 20,000 tablets 50 mg. The results demonstrate that sumatriptan tablets were preferred by a greater proportion of patients than sumatriptan injection. However, sumatriptan injection was perceived as the most effective dosing form by the greatest proportion of patients. Among patients who found sumatriptan injection to be the most effective dosing form, the most frequently cited reasons were efficacy and speed of action. Among patients who found sumatriptan tablets to be the most effective dosing form, the most frequently cited reasons were fewer side effects and lack of experience with other dosing forms. Approximately half of sumatriptan users indicated that sumatriptan use was associated with decreases in the numbers of days with migraine, days at work with migraine, and days off work/normal activities due to migraine. When they worked during a migraine attack, patients estimated that they were 76% effective after taking sumatriptan compared with 47% effective with other medications and 49% effective with no medication. In general, side effects were reported less frequently among sumatriptan tablet users compared with injection users. Asked to compare sumatriptan with the best migraine treatment that they had used before, 94% of patients indicated that sumatriptan was better or much better than their previous therapies. These data provide important information from the clinical practice setting to complement the data from sumatriptan clinical trials.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11279901&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Sumatriptan responsiveness and clinical, psychiatric and psychologic features in migraine patients.

Meckling SK, Becker WJ, Rose MS, Dalby JT.

Department of Clinical Neurosciences, University of Calgary, AB, Canada.

OBJECTIVE: To compare sumatriptan responders and nonresponders in a migraine population with regard to a number of clinical, psychiatric and psychologic features. METHODS: Patients were drawn from a referral headache clinic population, and classified as responders or nonresponders. Clinical features were assessed by a written questionnaire. The lifetime prevalence of several psychiatric disorders was determined by the National Institute of Mental Health diagnostic interview schedule and personality factors were measured by the 16 Personality Factors (16PF) Questionnaire. RESULTS: Nonresponders indicated less influence on their migraine by menstrual factors, had a higher lifetime prevalence of generalized anxiety, and showed 16PF scores indicating greater shyness, self-sufficiency and perfectionism. Nonresponders were also more imaginative and less socially outgoing. CONCLUSION: Although they must be interpreted with caution due to small sample size and the multiple comparisons made, our results indicate that there may be differences between sumatriptan responders and nonresponders with regard to a number of clinical, psychiatric and psychologic factors. These results suggest that biological differences exist between the two patient groups which likely account for both the differences in their responses to sumatriptan and in the clinical features noted above.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11766775&dopt=Abstract sumatriptan Imitrex