sumatriptan, Imitrex
Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack.

Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, and Department of Vascular Neurology, Faculty of Medicine, Semmelweis University, National Institute of Psychiatry and Neurology, Budapest, Hungary.

Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J & Bagdy G. Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalagia 2005; 25:179-183. London. ISSN 0333-1024Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP) concentration and headache intensity were investigated in 19 female migraineurs during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was administered 120 min after the onset of the attack. Blood samples were obtained immediately before and 60 min after sumatriptan administration. In those subjects whose migraine attack improved considerably 60 min after the treatment the plasma CGRP concentration decreased significantly (P < 0.05). In contrast, plasma CGRP concentration failed to change in patients whose headache did not improve. In addition, plasma CGRP concentrations showed significant positive correlations with the headache scores both 60 and 120 min after sumatriptan administration (P < 0.05). According to our results plasma CGRP concentration decreases parallel to headache intensity during sumatriptan treatment and this decrease in CGRP predicts effectiveness of antimigraine drug therapy. This supports that one of the main effects of triptans is to decrease CGRP release.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15689192&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines.

Friedman BW, Corbo J, Lipton RB, Bijur PE, Esses D, Solorzano C, Gallagher EJ.

Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA. befriedm montefiore.org

OBJECTIVE: To compare the efficacy of 20 mg of IV metoclopramide, given up to four times over 2 hours as needed for persistent headache, with 6 mg of subcutaneous sumatriptan for the emergency department treatment of migraine headaches. METHODS: This was a randomized, double-blind, clinical trial with two intervention arms. The primary endpoint was change in pain intensity as measured by an 11-point pain scale at 2 hours. Secondary endpoints included change in pain intensity at 24 hours and rates of pain-free headache relief at 2 and 24 hours. RESULTS: Two hundred two patients were screened, and 78 of 91 eligible patients were randomized. The two groups had comparable pain scores at baseline. By 2 hours, the change in pain intensity for the metoclopramide group was 7.2 compared with 6.3 for the sumatriptan group (95% CI for difference: -0.2 to 2.2). When compared at 24 hours, the metoclopramide group had improved by 6.1 compared with baseline and the sumatriptan group had improved by 5.0 (95% CI for difference: -0.6 to 2.8). At 2 hours, pain-free rates were 59% in the metoclopramide arm and 35% in the sumatriptan arm (95% CI for difference of 24%: 2 to 46%). The most common side effects at both time points were weakness, dizziness, and drowsiness, which were distributed evenly between the two groups. There were no reports of chest pain within the first 2 hours. The incidence of restlessness, stiffness, and abnormal movements was distributed equally between the two groups. CONCLUSIONS: When compared at 2 and 24 hours, aggressive (20 mg dosed up to four times) IV metoclopramide and 6 mg of subcutaneous sumatriptan relieved migraine headache pain comparably. Some secondary endpoints suggest that metoclopramide may be the preferable therapy for migraines presenting to the emergency department.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15699376&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Effects of a fast disintegrating/rapid release oral formulation of sumatriptan on functional ability in patients with migraine.

Barbanti P, Carpay JA, Kwong WJ, Ahmad F, Boswell D.

Department of Neurological Sciences, La Sapienza University, Rome, Italy.

BACKGROUND: A new oral form of sumatriptan has been developed to facilitate tablet disintegration and drug dispersion and to mitigate the effects of gastric stasis that can accompany migraine. OBJECTIVE: To evaluate the effects on functional ability of the new fast disintegrating/rapid release formulation of sumatriptan. METHODS: Sumatriptan 50 mg (n = 137), 100 mg (n = 142), or placebo (n = 153) was administered early when pain was mild for the acute treatment of a single migraine attack in a randomized, double-blind, parallel-group, placebo-controlled clinical trial. For this report, main health-outcomes endpoints (which were secondary endpoints for this clinical trial that was primarily designed to assess pain-free efficacy) included functional ability measured through 2 h postdose on a 5-point scale and lost time equivalents, a composite measure of migraine-associated time missed from activities, and reduced effectiveness at activities through 24 h postdose. RESULTS: Normal functional ability was restored in a significantly (p < 0.05) greater percentage of patients treated with sumatriptan than placebo beginning 45 min postdose for sumatriptan 100 mg and 1 h postdose for sumatriptan 50 mg. During the 24 h after initial dosing, the median (range) lost time equivalents for the combination of paid work activities and activities outside of paid work were significantly lower in the groups treated with sumatriptan (1.1 [0-10] sumatriptan 100 mg; 0.8 [0-36] sumatriptan 50 mg) compared with placebo (2.9 [0-24]) (p < or = 0.01 each sumatriptan group versus placebo). The corresponding mean +/- SD values for lost time equivalents were 1.9 +/- 2.3 and 2.5 +/- 4.7 for sumatriptan 100 mg and 50 mg, respectively, compared with 3.5 +/- 4.3 for placebo. CONCLUSION: A new oral sumatriptan formulation confers rapid, sustained restoration of functional ability in the acute treatment of migraine so that patients can return rapidly to normal functioning at work and outside of work.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15701219&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Triptans and the incidence of epithelial defects during laser in situ keratomileusis.

Hardten DR, Hira NK, Lombardo AJ.

Minnesota Eye Consultants, PA, Minneapolis, MN, USA. drhardten mneye.com

PURPOSE: To investigate whether the incidence of epithelial defects during laser in situ keratomileusis (LASIK) was different in patients who were taking sumatriptan (Imitrex, Glaxo Smith Kline, Pittsburgh, Pa) for migraine headaches than in those who were not. METHODS: A retrospective chart review was performed on 54 eyes of 28 patients who had been identified as taking sumatriptan and had undergone LASIK at Minnesota Eye Consultants between 1999 and 2001. These patients were compared with 54 gender- and age-matched control eyes operated on with the same microkeratome at the same location during the same period of time. The incidence of epithelial defects during LASIK was compared between the two groups. RESULTS: In the sumatriptan group, 11.1% (6 of 54) of eyes developed epithelial defects as compared to 9.3% (5 of 54) of eyes in the non-triptan group (P=.75, chi square). More recent sumatriptan exposure did not increase the incidence of epithelial defect (P=.47). In patients in whom sumatriptan was stopped >1 month prior to LASIK, 6.3% (1 of 16 eyes) had epithelial defects; in patients in whom sumatriptan was stopped <1 month prior to LASIK, 14.3% (4 of 28 eyes) developed epithelial defects; and 9.3% (5 of 54 eyes) of patients in whom no triptans had ever been used had epithelial defects (P=.70). CONCLUSIONS: There is no correlation between the use of sumatriptan for relief of migraine headaches and the generation of epithelial defects during LASIK. There appears to be no reason to stop triptans before proceeding with LASIK.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15724687&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Patterns of ergotamine and sumatriptan use in the Netherlands from 1991 to 1997.

Rahimtoola H, Egberts AC, Buurma H, Tijssen CC, Leufkens HG.

SIR Institute of Pharmacy Practice Research, Leiden, The Netherlands. h.rahimtoola pharm.uu.nl

The objective of this study was to assess usage patterns of ergotamine and sumatriptan over a period of 6 years, primarily to evaluate the impact that sumatriptan has had on the prescription of ergotamine. This study used ergotamine and sumatriptan prescription data representing inhabitants of eight cities in the Netherlands and covering the period of 1991-1997. The yearly incidence of new users between 1991 and 1997 was estimated for both drugs as well as for the drug of first choice to be prescribed to patients initiating specific abortive migraine treatment with either ergotamine or sumatriptan. Intra-individual ergotamine and sumatriptan usage patterns, characterized by single (incidental), continuous (rate of retention) or switch use, were examined for five patient cohorts, each for a follow-up period of 1 year. During the year of sumatriptan introduction (1991-1992), the overall incidence of new use for both drugs was highest (5.4 per 1000 inhabitants). Hereafter, a substantial reduction of more than 50% was observed. From 1992 to 1996, the yearly incidence of ergotamine first-time use was significantly higher than that of sumatriptan and up to 1996 ergotamine was more than twice as likely than sumatriptan to be prescribed to patients initiating specific abortive treatment. Hereafter, sumatriptan was as likely as ergotamine to be prescribed as the drug of first choice, which coincided with the full reimbursement of sumatriptan tablets. Overall, neurologists were more likely than general practitioners (GPs), to prescribe sumatriptan as the drug of first choice. Approximately half of the total study population were identified as single-time users. This phenomonen occurred more frequently in the ergotamine cohorts. The sumatriptan cohorts displayed a slight yet significant stronger retention rate compared with the ergotamine cohorts. The overall impact of sumatriptan on ergotamine use in The Netherlands was marginal, predominantly due to GP's adherence to migraine treatment guidelines and reimbursement policies concerning sumatriptan tablets. Overall, incidental use was relatively high and may reflect the reported difficulties in diagnosing migraine, lack of patient-doctor consultation, or that anticipated benefits of the drug were not achieved. Further study is required to clarify these issues.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11472386&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Vasoconstriction in human isolated middle meningeal arteries: determining the contribution of 5-HT1B- and 5-HT1F-receptor activation.

Razzaque Z, Heald MA, Pickard JD, Maskell L, Beer MS, Hill RG, Longmore J.

Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex.

AIMS: Sumatriptan is a 5-HT1B/1D-receptor agonist which also has affinity for 5-HT1F-receptors. The vasoconstrictor effects of sumatriptan are thought to be 5-HT1B-receptor mediated and these receptors have been shown to be expressed in human cranial blood vessels. However, in the same tissue mRNA coding for 5-HT1F-receptors has also been identified and this study addresses the possibility of whether 5-HT1F-receptor activation contributes to vasoconstriction. METHODS: The ability of two selective 5-HT1B/1D-receptor antagonists (GR125,743 and GR127,935) with no affinity for 5-HT1F-receptors, to inhibit sumatriptan evoked contractions in human isolated middle meningeal artery was investigated. Using a series of 5-HT1B/1D-receptor agonists (sumatriptan, zolmitriptan, CP122,288, L-741,519 and L-741,604), some with high affinity for 5-HTIF-receptors and the non-selective 5-HT-receptor agonists 5-HT and 5-CT, we compared the vasoconstrictor potency of these drugs in human isolated middle meningeal artery with their affinities at cloned human 5-HT1B-, 5-HT1D-and 5-HT1F-receptors expressed in CHO cell lines. RESULTS: GR125,743 antagonized sumatriptan evoked contractions in a competitive manner (apparent pA2 9.1) and GR127,935 antagonized sumatriptan-induced responses in a non-competitive manner (reducing the maximum contraction to 27%). There was a significant correlation between vasoconstrictor potency and 5-HT1B-receptor affinity (r=0.93, P=0.002) but not with 5-HT1D- or 5-HT1F-receptor affinity (r=0.74, P=0.06; r= 0.31, P= 0.49, respectively). CONCLUSIONS: These experiments show that in human middle meningeal artery vasoconstriction to sumatriptan-like agents is 5-HT1B-receptor mediated with little if any contribution from 5-HT1F-receptor activation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10073743&dopt=Abstract sumatriptan Imitrex



sumatriptan, Imitrex
Characterisation of the contractile activity of eletriptan at the canine vascular 5-HT1B receptor.

Gupta P, Scatchard J, Napier C, McHarg A, Wallis R.

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

The functional activity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]- 1 H-indole) at the contractile serotonin (5-hydroxytryptamine; 5-HT) '1B-like' receptor in dog isolated saphenous vein and basilar artery was investigated. Eletriptan, like 5-HT and sumatriptan potently contracted saphenous vein (pEC50: 6.3, 6.9 and 6.1, respectively) and basilar artery (pEC50 7.2, 7.5 and 6.8, respectively). The maximum responses evoked by eletriptan was, unlike sumatriptan, significantly lower than that to 5-HT (intrinsic activity saphenous vein: eletriptan 0.57, 5-HT 1.0, sumatriptan 0.85; basilar artery: eletriptan 0.77, 5-HT 0.98, sumatriptan 0.89). Contractions evoked by eletriptan were antagonised by the 5-HT1B/1D receptor antagonist GR125743 (N-[4-methoxy-3-(4-methyl piperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide) with pA2 values of 9.1 in saphenous vein and 9.4 in basilar artery. Affinity estimates (pKA) for 5-HT and sumatriptan determined from receptor alkylation studies in saphenous vein were 6.6 and 6.3, respectively, compared to the apparent equilibrium dissociation constant (pKp) for eletriptan of 6.8. The rank order of relative intrinsic efficacies (epsilon) was 5-HT > sumatriptan > eletriptan. Thus, eletriptan required greater receptor occupancy (4.4-fold) to evoke an equivalent contraction to 5-HT and sumatriptan in dog isolated saphenous vein. These data demonstrate that eletriptan is a potent partial agonist at the canine vascular 5-HT1B receptor.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10079003&dopt=Abstract sumatriptan Imitrex