sumatriptan, Imitrex
Autoradiographic mapping of [3H]sumatriptan binding in cat brain stem and spinal cord.

Mills A, Martin GR.

Receptor Pharmacology Group, Wellcome Research Laboratories, Beckenham, Kent, UK.

In vitro autoradiography was performed on sections of cat brain stem and spinal cord using [3H]sumatriptan. Localization studies using 20-25 nM [3H]sumatriptan showed specific binding to cells in the trigeminal nucleus caudalis and nucleus tractus solitarius of the brain stem and the dorsal horn of the spinal cord. This binding was unaffected by 8-hydroxy-dipropylaminotetralin (20 nM), but was abolished by 5-carboxamidotryptamine (200 nM). Ketanserin displaced total specific binding in the brain stem with a pIC50 of 6.2 but no apparent regional specificity. These results indicate that [3H]sumatriptan labels predominantly 5-HT1D alpha and/or 5-HT1D beta (but not 5-HT1A or 5-HT1F) receptor subtypes in cat brain stem and spinal cord.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7589183&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Quality of life assessment among migraine patients treated with sumatriptan.

Solomon GD, Skobieranda FG, Genzen JR.

Cleveland Clinic Headache Center, Department of General Internal Medicine, Cleveland (Ohio) Clinic Foundation 44195, USA.

PURPOSE--Quality of life evaluations can enhance traditional measures of therapeutic efficacy. The purpose of our study was to evaluate the impact of sumatriptan on the quality of life of patients with migraine headaches. PATIENTS AND METHODS--Migraine patients who were given a prescription for sumatriptan completed an SF-36 questionnaire and a nine-item pain questionnaire. Six to 9 months later, patients were mailed another copy of the SF-36 and the nine-item pain questionnaire. We compared the pretreatment and posttreatment scores for the SF-36 and for each question of the nine-item pain questionnaire. RESULTS--The pretreatment SF-36 was completed by 255 patients. The pretreatment pain questionnaire was completed by 86 of these patients. Follow-up questionnaires were returned by 147 patients (58%). Three of the eight SF-36 scales: role functioning--physical, bodily pain, and social functioning showed significant (P < 0.05) improvement with treatment. On the nine-item pain-specific questionnaire, three items--pain interference with normal work, ability to walk or move about, and enjoyment of life showed statistically significant (P < 0.05) improvement after sumatriptan treatment. CONCLUSIONS--Sumatriptan caused a significant improvement in the quality of life of patients with very severe migraine. This improvement was measurable by both the general quality of life instrument and the pain-specific questionnaire.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7591736&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
The pre- and postjunctional activity of CP-122,288, a conformationally restricted analogue of sumatriptan.

Beattie DT, Connor HE.

Glaxo Research and Development Ltd., Herts, UK.

The present study investigated the pre- and postjunctional of CP-122,288 (5-methyl-aminosulphonylmethyl-3-(N-methylpyrrolidin-2R-yl-m ethyl)-1H-indole), an analogue of the vascular 5-HT1 receptor agonist, sumatriptan. CP-122,288 inhibited neurogenic plasma protein extravasation in rat dura with a potency approximately 40,000-fold greater than sumatriptan (ID50 values of 0.3 pmol/kg and 13.9 nmol/kg i.v. respectively). However, CP-122,288 was only approximately 2-fold more potent than sumatriptan at inhibiting neurogenically mediated contractions of the dog saphenous vein. CP-122,288 contracted the dog saphenous vein and basilar artery with a potency approximately 2-fold greater than that of sumatriptan. Both compounds possessed similar affinities at either human 5-HT1D alpha or 5-HT1D beta receptors. It is concluded that CP-122,288 exhibits a prejunctional selectivity in the meninges to inhibit dural plasma protein extravasation independent of 5-HT1D alpha and 5-HT1D beta receptor activation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7601213&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Comparison of the effects of sumatriptan and the NK1 antagonist CP-99,994 on plasma extravasation in Dura mater and c-fos mRNA expression in trigeminal nucleus caudalis of rats.

Shepheard SL, Williamson DJ, Williams J, Hill RG, Hargreaves RJ.

Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, U.K.

Dural plasma extravasation produced by electrical stimulation of the trigeminal ganglion was measured in rats and the concomitant expression of c-fos mRNA produced in the trigeminal nucleus caudalis (NtV) was measured using in situ hybridization techniques. The non-peptide NK1 receptor selective antagonist CP-99,994 (1-3000 micrograms kg-1) and the 5HT1D receptor agonist sumatriptan (1-1000 micrograms kg-1) reduced dural plasma extravasation dose-dependently with ID50S of 52 micrograms kg-1 and 30 micrograms kg-1 respectively. CP-99,994 (1000 micrograms kg-1). a compound known to have good brain penetration, decreased c-fos mRNA expression in the NtV by 37 +/- 7% without disruption of the blood brain barrier (BBB). Sumatriptan (1000 micrograms kg-1), known to be poorly brain penetrant, had no significant effect on c-fos mRNA expression in the NtV unless the BBB was disrupted by infusion of a hyperosmolar mannitol solution after which sumatriptan decreased c-fos mRNA expression by 65 +/- 11%. The results suggest that brain penetrant NK1 receptor antagonists may have anti-migraine effects peripherally through blockade of dural extravasation and centrally by inhibition of nociceptive pathways. Furthermore the data indicates that the anti-migraine action of sumatriptan must be predominantly peripherally mediated, be it via inhibition of plasma extravasation or direct vasoconstriction, since it had little effect on the activation of neurones in the NtV unless the BBB was disrupted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7630480&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
[A comparison of the effects of serotonin, 2-(2-aminoethyl)quinoline (D-1997) and sumatriptan on the external carotid blood flow in the dog]

[Article in Spanish]

Terron JA, Ramirez-San Juan E, Villalon CM.

Departamento de Farmacologia y Toxicologia, Centro de Investigacion y de Estudios Avanzados del I.P.N., Mexico, D. F., Mexico.

The quinoline derivative, 2-(2-aminoethyl)-quinoline (D-1997) has been shown to mimic the contractile effects induced by serotonin (5-hydroxytryptamine; 5-HT) in the saphenous vein and basilar artery of the dog. Inasmuch as the receptor mechanisms mediating the above effects are similar to those involved in 5-HT-induced vasoconstriction of the canine common carotid circulation, the present study was set out to analyze the haemodynamic profile of D-1997 in the canine external carotid vascular bed. The effects of D-1997 were compared with those produced by 5-HT and the antimigraine drug, sumatriptan. One-min intracarotid (i.c.) infusions of D-1997 (10, 30, 100, 300 and 1000 micrograms/min), 5-HT (0.3, 1, 3, 10, 30 and 100 micrograms/min) and sumatriptan (3, 10, 30 and 100 micrograms/min) elicited dose-dependent decreases in external carotid blood flow (ECBF); since the infusions of agonists did not modify arterial blood pressure, they produced dose-dependent increases in external carotid resistance (ECR). The vasoconstrictor responses to D-1997 and 5-HT were of short duration (up to 10 min) whilst those to sumatriptan were longer lasting (up to 40 min). In addition, the effects induced by the agonists in the external carotid bed did not affect basal resistance in the contralateral common carotid, thereby suggesting a local effect by D-1997. The rank order of agonist potency was 5-HT > sumatriptan > D-1997; however, the order of agonist efficacy, represented as the maximum response obtained with the highest dose, displayed a different pattern, namely, D-1997 > or = sumatriptan > 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7639592&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Cost savings in migraine associated with less chest pain on new triptan therapy.

Wang JT, Barr CE, Torigoe Y, Wang E, Rowland CR, Goldfarb SD.

Pharmacia Corporation, Peapack, New Jersey, USA.

OBJECTIVES: This article constructs an economic model to estimate cost of chest-pain-related care in migraine patients receiving almotriptan 12.5 mg compared with those receiving sumatriptan 50 mg. STUDY DESIGN: This population-based, retrospective cohort study used data from the MEDSTAT Marketscan database (Ann Arbor, Michigan) to quantify incidence and costs of chest-pain-related diagnoses and procedures. After a 6-month exclusion period, the study used a pre-post design, with baseline and treatment periods defined, respectively, as 5 months before and after receiving sumatriptan therapy. An economic model was constructed to estimate annual cost savings per 1,000 patients receiving almotriptan instead of sumatriptan as a function of differing rates of chest pain. Annual direct medical cost avoided was calculated for a hypothetical health plan covering 1 million lives. RESULTS: Among a cohort of 1,390 patients, the incidence of chest-pain-related diagnoses increased significantly (43.6%) with sumatriptan, from 110 during the baseline period to 158 during the treatment period (P= .003). Aggregate costs for chest-pain-related diagnoses and procedures increased 33.1%, from $22,713 to $30,234. Payments for inpatient hospital services rose 10-fold; costs for primary care visits and outpatient hospital visits rose 53.1% and 14.4%, respectively. Payments for angiography increased from $0 to $462, and costs for chest radiographs and electrocardiograms increased 58.7% and 31.2%, respectively. Sumatriptan treatment was associated with a 3-fold increase in payments for services for painful respiration and other chest pain. The model predicted $11,215 in direct medical cost savings annually per 1000 patients treated with almotriptan instead of sumatriptan. Annual direct medical costs avoided for the health plan totaled $195,913. CONCLUSION: Using almotriptan instead of sumatriptan will likely reduce the cost of chest-pain-related care for patients with migraine headaches.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11859905&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
[Sumatriptan and cluster headache]

[Article in Spanish]

Moreno A, Serrano V, Casado JL, Arenas C, Alberca R.

Servicio de Neurologia, Hospital Universitario Virgen del Rocio, Sevilla.

Double-blind studies have demonstrated the efficacy of sumatriptan for the treatment of cluster headache (CH) but little is known about its use on a daily basis. The open trial reported here analyzed the efficacy, tolerance and appropriateness of subcutaneous administration of sumatriptan; the results are compared with findings for other treatments of CH. Sumatriptan was used in 232 attacks suffered by 16 patients and its effect was very rapid. Pain began to diminish a mean 9 minutes after injection and the most intense had disappeared in less than 15 minutes. All the patients preferred sumatriptan to other treatments. No serious side effects were recorded and the patients were satisfied with subcutaneous injection. Sumatriptan was considered the first choice medication for treatment of CH symptoms, although its high cost is a drawback that had to be taken into account.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7695947&dopt=Abstract sumatriptan Imitrex