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PubMed2000

No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery.

1. Using subtype-selective 5-HT1 receptor agonists and/or the 5-HT1 receptor antagonist GR127935, we characterized in vitro the 5-HT receptor that mediates the contraction of human and bovine cerebral arteries. Further, we investigated which sumatriptan-sensitive receptors are present in human coronary artery by reverse-transcriptase polymerase chain reaction (RT-PCR). 2. Agonists with affinity at the 5-HT1B receptor, such as sumatriptan, alniditan and/or IS-159, elicited dose-dependent contraction in both human and bovine cerebral arteries. They behaved as full agonists at the sumatriptan-sensitive 5-HT1 receptors in both species. In contrast, PNU-109291 and LY344864, selective agonists at 5-HT1D and 5-HT1F receptors, respectively, were devoid of any significant vasocontractile activity in cerebral arteries, or did not affect the sumatriptan-induced vasocontraction. The rank order of agonist potency was similar in both species and could be summarized as 5-HT = alniditan > sumatriptan = IS-159 >>> PNU-109291 = LY344864. 3. In bovine cerebral arteries, the 5-HT1 receptor antagonist GR127935 dose-dependently inhibited the vasoconstrictions elicited by both 5-HT and sumatriptan, with respective pA2 values of 8.0 and 8.6. 4. RT-PCR studies in human coronary arteries showed a strong signal for the 5-HT1B receptor while message for the 5-HT1F receptor was weak and less frequently detected. Expression of 5-HT1D receptor mRNA was not detected in any sample. 5. The present results demonstrate that the triptan-induced contraction in brain vessels is mediated exclusively by the 5-HT1B receptor, which is also present in a majority of human coronary arteries. These results suggest that selective 5-HT1D and 5-HT1F receptor agonists might represent new antimigraine drugs devoid of cerebro- and cardiovascular effects.

Animals↗

PubMed2001

Vascular effects of the new anti-migraine agent almotriptan on human cranial and peripheral arteries.

This paper describes the vascular effects of almotriptan in comparison with sumatriptan in human vessels and tissues in vitro. The contractile properties of almotriptan and sumatriptan were evaluated in vitro in the following arteries: meningeal, temporal, basilar, internal carotid, ophthalmic, pulmonary and coronary. In addition, the effects of almotriptan on the pulmonary vein and on bronchial tissues were studied. Almotriptan showed selectivity of action for migraine-related arteries (i.e. contractile EC(50) of 30 and 700 nm for meningeal and temporal arteries, respectively), whereas the effect on arteries supplying blood to the brain was lower. The contractile effect of almotriptan was lower than that of sumatriptan in pulmonary arteries, whereas in bronchial preparations no clinically relevant contractile responses were observed for either almotriptan or sumatriptan. In ophthalmic arteries the contractile effects of almotriptan and sumatriptan were similar, whereas lower contractile effects were obtained with almotriptan than with sumatriptan in coronary arteries.

Arteries↗

PubMed1996

Drug treatment of migraine: acute treatment and migraine prophylaxis.

Most current randomised controlled trials concern the acute treatment of migraine. Sumatriptan, a serotonin receptor agonist, was evaluated in 8 randomised controlled trials. Using a novel cartridge self-injector system subcutaneous sumatriptan was found superior to placebo, and oral sumatriptan in doses from 25 mg to 100 mg was found superior to placebo with no difference among doses. An oral dose of 100 mg sumatriptan was not superior to a combination of lysine acetylsalicylate plus metoclopramide, and 100 mg sumatriptan given 4 hrs after subcutaneous sumatriptan could not prevent recurrence of headache. Nasal dihydroergotamine was found to have some efficacy in acute migraine treatment, whereas nasal butorphanol, although effective in repeated doses, was hampered by many side effects. The prophylactic effect of valproate was confirmed in one randomised controlled trial.

Humans↗

PubMed2006

Functional reactivity of 5-HT receptors in human umbilical cord and maternal subcutaneous fat arteries after normotensive or pre-eclamptic pregnancy.

OBJECTIVE: To investigate the functional reactivity of 5-hydroxytryptamine (serotonin; 5-HT) receptors in foetal umbilical cord arteries (UCA) and maternal subcutaneous fat resistance arteries (SFA) in normotensive and pre-eclamptic pregnancy. DESIGN: Study groups were divided based on the presence or absence of pre-eclampsia and the duration of gestation. METHODS: Segments of UCA and SFA were mounted in tissue baths and concentration-response curves to 5-HT and sumatriptan (5-HT1B/1D receptor agonist) were constructed in the absence or presence of ketanserin (5-HT2A receptor antagonist) or GR125743 (5-HT1B/1D receptor antagonist). RESULTS: Both 5-HT and sumatriptan contracted all UCA segments studied. The responses to 5-HT and the potency of ketanserin in UCA were not different between the study groups, indicating a similar profile of the 5-HT2A receptor. In contrast, the potencies of sumatriptan and GR125743 were significantly higher in normotensive full-term pregnancies than in normotensive pre-term pregnancies in UCA. The response to sumatriptan in UCA arteries was not significantly different between pre-eclamptic and normotensive pregnancies. However, the potency of both sumatriptan and GR125743 was positively correlated to the gestational age in the normotensive group, whereas this relationship was absent in the pre-eclamptic group. In SFA, responses to 5-HT and sumatriptan were not different between the pre-eclamptic patients and normotensive controls. CONCLUSIONS: In both UCA and SFA, 5-HT1B/1D and 5-HT2A receptors mediate vasoconstriction. The sensitivity of 5-HT1B/1D receptors increases in the last trimester in the UCA in normal pregnancies, which seems to be expedited in pre-eclamptic patients. Further studies on 5-HT1B/ID receptors will thus give new insights into the foetal development and pathophysiology of pre-eclampsia.

Adult↗

PubMed2004

5-Hydroxytryptamine1B receptor-mediated contraction of rabbit saphenous vein and basilar artery: role of vascular endothelium.

This study characterizes the sumatriptan-sensitive [5-hydroxytryptamine (5-HT)(1B/1D)] receptor in rabbit saphenous vein and basilar artery. (S)-(-)-1-[2-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-ethyl]isochroman-6-carboxylic acid methylamide (PNU-109291), a 5-HT(1D) subtype-selective agonist (human K(i) = 2.5 +/- 0.07 nM), did not contract either tissue, whereas o-methoxyphenylpiperazide derivative 4F (MPPA-4F), a 5-HT(1B) subtype-selective antagonist (human K(i) = 4.6 +/- 0.6 nM) potently inhibited sumatriptan-induced contraction in the saphenous vein and basilar artery. These results suggested that sumatriptan-induced contraction was mediated via the 5-HT(1B) receptor in these blood vessels. 5-HT(1B) receptor-mediated contraction was then compared in endothelium-intact and denuded vessels to evaluate the role of the endothelium in regulating sumatriptan-induced contractility in these tissues. The presence of an intact endothelium inhibited 5-HT(1B)-induced contraction in both tissues. Endothelial denudation or nitric-oxide synthase inhibition with N(omega) nitro-L-arginine methyl ester (L-NAME) (100 microM) increased the efficacy and potency of sumatriptan in the saphenous vein and basilar artery. Surprisingly, in endothelial-denuded vascular tissues, L-NAME (100 microM) also significantly increased the maximal 5-HT(1B) receptor-induced contraction in both tissues, with no effect on potency of sumatriptan. The effect of L-NAME after endothelial denudation may reflect the presence of a low density of residual endothelial cells as estimated by CD31 antibody staining combined with the modulating effect of nitric oxide released from nonendothelial cells in vascular tissue. Endothelial modulation was specific to 5-HT(1B) receptors because removal of the endothelium did not significantly alter contraction to norepinephrine, histamine, prostaglandin, or potassium chloride in the saphenous vein or basilar artery.

Animals↗

PubMed1998

5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans.

The selective 5-hydroxytryptamine-1 receptor agonist sumatriptan inhibits exocrine pancreatic function in humans. No data are available on the effect of sumatriptan on fasting and postprandial endocrine pancreatic function in humans. To elucidate the influence of 5-hydroxytryptamine-1 receptor activation by sumatriptan on endocrine pancreatic function and blood glucose homeostasis, we determined plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin, and C-peptide before and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers, and we measured blood glucose and insulin plasma levels during an oral glucose tolerance test after placebo and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers. Sumatriptan significantly decreased the mean plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin and C-peptide (P < 0.001) and also significantly decreased mean and peak plasma levels of insulin after an oral glucose challenge (P < 0.02 and P = 0.04, respectively) without affecting glucose homeostasis. From our study, we speculate that activation of the 5-hydroxytryptamine-1 receptor inhibits endocrine pancreatic secretion.

Adult↗

PubMed2005

Pharmacological challenge with a serotonin 1D agonist in alcohol dependence.

BACKGROUND: Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink. METHODS: Fifteen patients with alcohol dependence who had undergone detoxification were recruited. Sumatriptan (100 mg) and placebo was administered in cross-over fashion on 2 separate days 72 hours apart. Both patients and raters were blind to all treatments. Patients were assessed on the following scales at -30, 0, 30, 90, 150 and 210 minutes: A 6-item scale designed to rate the patient's intention to drink; The Sensation Scale; a 13-item affect analog scale designed to rate the pattern and extent of emotional changes; and an 8-item scale designed to rate the patient's craving for alcohol. RESULTS: No significant differences were found between the placebo and sumatriptan groups and no significant cross over effects were found. CONCLUSION: The general lack of efficacy of sumatriptan in producing alcohol-like symptoms or a desire to drink alcohol may suggest that the 5HT1D receptor plays little role in the pathophysiology of alcoholism.

Alcohol Drinking↗

PubMed2005

Symptomatic treatment of migraine in children: a systematic review of medication trials.

OBJECTIVE: Treatment of pediatric migraine includes an individually tailored regimen of both nonpharmacologic and pharmacologic measures. The mainstay of symptomatic treatment in children with migraine is intermittent oral or suppository analgesics, but there is no coherent body of evidence on symptomatic treatment of childhood migraine available. The objective of this review is to describe and assess the evidence from randomized and clinical controlled trials concerning the efficacy and tolerability of symptomatic treatment of migraine in children. DESIGN: Systematic review according to the standards of the Cochrane Collaboration. METHODS: Databases were searched from inception to June 2004. Additional reference checking was performed. Two authors independently selected randomized and controlled trials evaluating the effects of symptomatic treatment in children (<18 years old) with migraine, using headache (HA) clinical improvement as an outcome measure. Two authors assessed trial quality independently by using the Delphi list, and data were extracted from the original reports by using standardized forms. Quantitative and qualitative analysis was conducted according to type of intervention. RESULTS: A total of 10 trials were included in this review, of which 6 studies were considered to be of high quality. The number of included participants in each trial ranged from 14 to 653, with a total of 1575 patients included in this review. Mean dropout rate was 19.8% (range: 0-39.1%), and the mean age of participants was 11.7 +/- 2.2 years (range: 4-18 years). All studies used HA diaries to assess outcomes. In most studies, a measure of clinical improvement was calculated by using these diaries. Improvement often was regarded as being clinically relevant when the patients' HA declined by > or =50%. Regarding oral analgesic treatment, the effectiveness of acetaminophen, ibuprofen, and nimesulide were evaluated. When compared with placebo, acetaminophen (relative risk [RR]: 1.5; 95% confidence interval [CI]: 1.0-2.1) and ibuprofen (pooled RR: 1.5; 95% CI: 1.2-1.9) significantly reduced HAs. We conclude that there is moderate evidence that both acetaminophen and ibuprofen are more effective in reduction of symptoms 1 and 2 hours after intake than placebo with minor adverse effects. No clear differences in effect were found between acetaminophen and ibuprofen or nimesulide. Regarding the nonanalgesic interventions, nasal-spray sumatriptan, oral sumatriptan, oral rizatriptan, oral dihydroergotamine, intravenous prochlorperazine, and ketorolac were evaluated. When compared with placebo, nasal-spray sumatriptan (pooled RR: 1.4; 95% CI: 1.2-1.7) seemed to significantly reduce HAs. We conclude that there is moderate evidence that nasal-spray sumatriptan is more effective in reduction of symptoms than placebo but with significantly more adverse events. No differences in effect were found between oral triptans and placebo. All medications were well tolerated, but significantly more adverse events were reported for nasal-spray sumatriptan compared with placebo. We also conclude that there is moderate evidence that intravenous prochlorperazine is more effective than intravenous ketorolac in the reduction of symptoms 1 hour after intake. No differences in effect were found between oral dihydroergotamine and placebo. CONCLUSIONS: Acetaminophen, ibuprofen, and nasal-spray sumatriptan are all effective symptomatic pharmacologic treatments for episodes of migraine in children. The new frontier for symptomatic treatment is likely to be the development of triptan agents for use in children. Most treatments have only been evaluated in 1 or 2 studies, which limits the generalizability of the findings. We strongly recommend performing a large, high-quality randomized, controlled trial evaluating different symptomatic medications compared with each other or to placebo treatment. Favorable high-quality studies should be performed and reported according to the CONSORT statement. Clinical improvement of HA should be used as the primary outcome measure, but quality of life, days missed at school, and satisfaction of child or parents should also be used as an outcome measure in future studies.

Acetaminophen↗

PubMed1999

Regulation of calcitonin gene-related peptide secretion by a serotonergic antimigraine drug.

We have investigated the regulation of calcitonin gene-related peptide (CGRP) release from trigeminal neurons by the serotonergic antimigraine drug sumatriptan. Serum levels of the neuropeptide CGRP are elevated during migraine. Treatment with the drug sumatriptan returns CGRP levels to normal coincident with the alleviation of headache. However, despite this clinical efficacy, the cellular target and mechanism of sumatriptan action are not well understood beyond the pharmacology of its recognition of the 5-HT1 class of serotonin receptors. We have used cultured trigeminal neurons to demonstrate that sumatriptan can directly repress CGRP secretion from sensory neurons. The stimulated secretion in response to depolarization or inflammatory agents was inhibited, but not the basal secretion rate. Unexpectedly, sumatriptan did not lower cAMP levels, in contrast to the classical role ascribed to the 5-HT1 receptors. Instead, activation of 5-HT1 receptors caused a slow and remarkably prolonged increase in intracellular calcium. The inhibition of CGRP secretion is attenuated by the phosphatase inhibitor okadaic acid, suggesting that sumatriptan action is mediated by calcium-recruited phosphatases. These results suggest that 5-HT1 agonists may block a deleterious feedback loop in migraine at the trigeminal neurons and provide a general mechanism by which this class of drugs can attenuate stimulated neuropeptide release.

Animals↗

PubMed2000

Rational migraine management: optimising treatment with the triptans.

In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have been approved for marketing in most countries of the world (naratriptan, rizatriptan and zolmitriptan). In addition, at least three others are in advanced stage of clinical development (almotriptan, eletriptan, and frovatriptan). This paper sets out to review the recent data with the aim of identifying: 1) What are the critical differences between the TELs and sumatriptan? 2) How do the currently licensed TELs compare? 3) Is it possible to provide a rational approach to migraine therapy based on objective differences in the clinical profile of these new drugs? Recent randomised controlled and comparator data were reviewed, including the independent FDA assessment of rizatriptan. Critical differences for the new TELs (naratriptan, rizatriptan and zolmitriptan) which may lead to more rational migraine management: Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5.0 mg) have demonstrated superior efficacy to sumatriptan 100 mg, and 25 and 50 mg respectively. Therefore, for first line use either rizatriptan or zolmitriptan would be appropriate for moderate and severe headache. Rizatriptan has a more rapid onset of action than sumatriptan 100 mg. Both rizatriptan and zolmitriptan have a more rapid onset of action than naratriptan. Therefore, for a rapid onset of action either rizatriptan or zolmitriptan would be appropriate. Naratriptan would appear to have a lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. However, 24-hour efficacy rates for zolmitriptan 2.5 mg were significantly greater than for sumatriptan 25 mg and 50 mg and were not significantly different from naratriptan. Therefore, for headaches of long duration and with a tendency to recur (e.g. menstrual headaches) either naratriptan or zolmitriptan would be appropriate. Naratriptan has lower reported adverse event rates comparable with placebo. This would support the use of naratriptan 2.5 mg in patients who have demonstrated poor tolerance to the "triptan type" adverse events.

Humans↗

PubMed1999

Diclofenac-potassium in migraine: a review.

UNLABELLED: The NSAID diclofenac is a potent inhibitor of prostaglandin synthesis and an established antipyretic and analgesic agent. Diclofenac-potassium was developed as an immediate-release tablet with the aim of providing rapid onset of action after oral administration. This formulation has been investigated in the acute treatment of migraine. Data from available placebo-controlled clinical trials indicate that diclofenac-potassium 50 or 100mg as an immediate-release tablet is more effective than placebo and as effective as oral sumatriptan 100mg and ergotamine plus caffeine at reducing pain intensity in patients with migraine 2 hours after initial administration. Duration of pain relief is similar for the 3 drugs but onset appears to be faster with diclofenac-potassium than with oral sumatriptan or ergotamine plus caffeine. Diclofenac-potassium appears to have favourable effects on some accompanying symptoms such as nausea and vomiting. The frequency of these symptoms was significantly lower with diclofenac-potassium than with sumatriptan in 1 study, although only a few patients had vomiting at baseline. Effects on phonophobia or photophobia did not differ between diclofenac-potassium, sumatriptan and ergotamine plus caffeine. The need for rescue medication is consistently less with diclofenac-potassium than with placebo. Data are inconsistent or scarce regarding the effects of diclofenac-potassium versus placebo on other measures such as headache recurrence and working ability. Diclofenac-potassium was generally well tolerated in clinical trials in patients with migraine. Adverse events reported most frequently (abdominal pain, tiredness and fatigue and nausea) were typically mild to moderate. CONCLUSION: Diclofenac-potassium provides rapid pain relief (within 60 to 90 minutes), is well tolerated and reduces the frequency of some of the accompanying symptoms in patients with migraine. Available trials indicate that diclofenac-potassium provides similar pain relief to sumatriptan and is at least as effective as ergotamine plus caffeine, but appears to have a greater effect on nausea and vomiting than sumatriptan and a faster onset of action than both drugs. Comparisons with other NSAIDs are lacking. Diclofenac-potassium is likely to find a role as a useful first-line option in the acute treatment of migraine.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Almotriptan: a review of its use in migraine.

UNLABELLED: Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient, and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. CONCLUSIONS: Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (<or=1 year). Almotriptan has a good adverse event profile and a generally similar overall tolerability profile to sumatriptan; of note, almotriptan is associated with a significantly lower incidence of chest pain than sumatriptan. However, further clinical experience is required to clearly define the place of almotriptan among the other currently available triptans. Nevertheless, because triptans have an important place in various management regimens, and because the nature of individual patient response to triptans is idiosyncratic, almotriptan is likely to become a useful treatment option in the management of adults with moderate or severe migraine headaches.

Animals↗

PubMed2002

Spotlight on almotriptan in migraine.

UNLABELLED: Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. CONCLUSIONS: Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (< or = 1 year). Almotriptan has a good adverse event profile and a generally similar overall tolerability profile to sumatriptan; of note, almotriptan is associated with a significantly lower incidence of chest pain than sumatriptan. However, further clinical experience is required to clearly define the place of almotriptan among the other currently available triptans. Nevertheless, because triptans have an important place in various management regimens, and because the nature of individual patient response to triptans is idiosyncratic, almotriptan is likely to become a useful treatment option in the management of adults with moderate or severe migraine headaches.

Clinical Trials as Topic↗

PubMed2002

Health outcomes evaluations: estimating the impact of almotriptan in managed care settings.

OBJECTIVE: Almotriptan, a new treatment for acute migraine attacks, may improve health outcomes while reducing expenditures on drug costs and the costs associated with unwanted adverse events. This article describes the clinical, humanistic, and economic data available for almotriptan and compares these data with published data for sumatriptan, which is considered the gold standard comparator for triptans. PATIENTS AND METHODS: Clinical trial data and published materials describing the pharmacoeconomics of sumatriptan were reviewed. RESULTS: Formulary and prescribing decision makers consider clinical, humanistic, and economic dimensions when evaluating migraine treatments. Within those dimensions, critical elements to consider include efficacy, tolerability, health-related quality of life, patient satisfaction, productivity, medication cost, and healthcare resource use. In direct comparisons, almotriptan has demonstrated efficacy, short-term health-related quality of life, and productivity results similar to sumatriptan 50 mg. Almotriptan also has an improved tolerability profile compared with sumatriptan, including a lower incidence of drug-related adverse events, a lower incidence of chest pain, and better patient satisfaction in terms of adverse events. CONCLUSIONS: Almotriptan and sumatriptan exhibit comparable efficacy for the treatment of acute migraine. The acquisition cost of almotriptan is lower than sumatriptan, and given its excellent tolerability profile, almotriptan may be preferred by patients for the treatment of migraine attacks.

Cost Control↗

PubMed2006

[Symptomatic treatment of migraine with zolmitriptan: experience with 82 patients].

OBJECTIVES: To analyze our experience with the new, 5 mg intranasal formulation of zolmitriptan in the symptomatic treatment of migraine attacks. PATIENTS AND METHODS: This series includes 82 patients who had treated an average of 7 migraine attacks. Eighty patients had taken oral triptans and 20 subcutaneous sumatriptan. The main reasons for using nasal zolmitriptan were: poor efficacy of oral triptans (41.5 % of the patients), use of subcutaneous sumatriptan (24.4%) or medical criteria (34.5%). RESULTS: Among the 80 patients who had been treated with oral triptans, 50 (62.5 %) preferred nasal zolmitriptan, 14 (17.5 %) oral triptans and the remaining 16 (20 %) did not express any preference. The main reasons for this preference were shorter speed of action and better efficacy. Within those 20 patients who were using subcutaneous sumatriptan, 8 (40 %) preferred subcutaneous sumatriptan, 5 (25%) nasal zolmitriptan and 7 (35%) did not express any preference. The reasons for preference of intranasal zolmitriptan over subcutaneous sumatriptan were greater convenience, better tolerability and lower price. A total of 55 patients noticed efficacy within 60 min. Half experienced at least one adverse event, always mild. The most frequent were local: bad taste (n=23) or nasal irritation/itching (n=8). CONCLUSIONS: The new intranasal formulation of 5 mg zolmitriptan is a good option for the symptomatic treatment of migraine, which could be considered as an intermediate between oral triptans and the subcutaneous formulation of sumatriptan.

Administration, Intranasal↗

PubMed1992

5-HT1-like receptor mediated changes in porcine carotid haemodynamics: are 5-HT1D receptors involved?

5-Hydroxytryptamine (5-HT) reduces porcine arteriovenous shunting in the carotid vascular bed by stimulation of both 5-HT1-like and 5-HT2 receptors and increases capillary flow to some tissues, like the skin and ears, by different 5-HT1-like receptors. In view of the heterogeneous nature of the 5-HT1-like receptors and the relative selectivity for the 5-HT1D binding sites of sumatriptan, which also reduces porcine arteriovenous shunting and slightly increases capillary blood flow towards skin and ears by 5-HT1-like receptors, we have attempted to determine whether one or both of these carotid 5-HT1-like receptors belong to the 5-HT1D subtype. Pentobarbitone anaesthetized pigs, subjected to bilateral cervical vagosympathectomy, received either 5-HT (2 micrograms.kg-1.min-1) in the carotid artery or cumulative i.v. doses of sumatriptan (10, 30, 100 and 300 micrograms.kg-1). Their effect on the total carotid blood flow and its distribution into capillary and arteriovenous anastomotic parts was determined with radioactive microspheres. The effect of metergoline (1 mg.kg-1), a substance with a very high affinity for the 5-HT1D receptor as well as for the 5-HT1A, 5-HT1B, 5-HT1C and 5-HT2 receptors, was studied on the responses to 5-HT and sumatriptan. Both 5-HT and sumatriptan reduced carotid arteriovenous anastomotic blood flow. 5-HT and, to a lesser extent, sumatriptan also increased capillary blood flow towards some tissues. Metergoline by itself did not affect the distribution of porcine carotid blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Operational characteristics of the 5-HT1-like receptors mediating external carotid vasoconstriction in vagosympathectomized dogs. Close resemblance to the 5-HT1D receptor subtype.

It has recently been shown that the external carotid vasoconstrictor response to 5-HT in the dog is primarily mediated by sumatriptan-sensitive 5-HT1-like receptors; however, the fact that these receptors are not blocked by metergoline, a 5-HT1D ligand, raises questions about their possible correlation with the 5-HT1D receptor subtype. Since a number of drugs display high affinity for the 5-HT1D (GR127935) and 5-HT1F (e.g. methysergide and oxymetazoline) receptor subtypes, in this study we have used these drugs to determine whether the above vasoconstrictor 5-HT1-like receptors correlate with the 5-HT1D and/or 5-HT1F receptor subtypes. One-minute intracarotid infusions of 5-HT (0.3-30 micrograms/min), sumatriptan (1-30 micrograms/min), oxymetazoline (0.03-3 micrograms/min) and noradrenaline (0.3-3 micrograms/min) resulted in dose-dependent decreases in external carotid blood flow without changes in arterial blood pressure or heart rate. These vasoconstrictor responses remained unaltered after i.v. administration of physiological saline (0.015, 0.05 and 0.15 ml/kg; n = 4) or ritanserin (1 mg/kg; n = 5). In contrast, GR127935 (1, 3 and 10 micrograms/kg, n = 6) potently blocked the responses to 5-HT (unmasking a dose-dependent vasodilator component) and sumatriptan without affecting those to oxymetazoline or noradrenaline. Interestingly, methysergide (10, 30 and 100 micrograms/kg, n = 5) also blocked the vasoconstrictor responses to 5-HT and sumatriptan, but unlike GR127935, did not revert the vasoconstrictor response to 5-HT; the responses to oxymetazoline remained unaffected, but those to noradrenaline were apparently attenuated by the highest dose. Taken together, the above findings suggest that the sumatriptan-sensitive 5-HT1-like receptors mediating canine external carotid vasoconstriction resemble 5-HT1D receptors, probably of the 5-HT1D beta subtype on the basis of the resistance to blockade by ritanserin. The pharmacological profile of these receptors could be similar (bovine and human cerebral arteries, porcine carotid arteriovenous anastomoses and human coronary arteries) to other putative 5-HT1D receptors mediating vascular responses.

Analysis of Variance↗

PubMed1995

5-HT1-like and 5-HT2A receptors mediate 5-hydroxytryptamine-induced contraction of rabbit isolated mesenteric artery.

The contractions induced by 5-hydroxytryptamine (5-HT) and the 5-HT1-like receptor agonist, sumatriptan, were investigated in the open ring preparations of rabbit mesenteric artery in order to characterize the 5-HT receptors. 5-HT induced concentration-dependent contractions. Sumatriptan did not induce any contraction of unstimulated rings, whereas it elicited concentration-dependent contractions in preparations given a moderate tone by a threshold concentration of prostaglandin F2 alpha (PGF2 alpha). Pargyline, cocaine or normetanephrine were without significant effect on the contractions induced by 5-HT and sumatripan. The 5-HT concentration-effect curve was clearly biphasic. Methiothepin (0.01 microM) shifted the both phases of the concentration-effect curve to the right. Ketanserin (0.1 microM) shifted the second, low affinity, phase and prazosin did not alter concentration-effect curve to 5-HT. The sumatriptan concentration-effect curve was shifted by methiothepin (0.01 microM) to the right (pKB = 9.19) but not by ketanserin (1 microM). Concentration-effect curves to 5-HT and sumatriptan were not affected by the 5-HT3 receptor antagonist tropisetron (1 microM). These results suggest that 5-HT1-like type receptors are responsible for the first phase of 5-HT-induced contraction and 5-HT2A receptor for the second phase, in rabbit mesenteric artery. Sumatriptan-induced contractions appear to be mediated by 5-HT1-like type receptors in this artery. These results also suggest that this kind of amplification may be a common feature of vascular 5-HT1-like type receptor as has been shown in other vascular segments such as rabbit femoral, iliac and renal arteries, and guinea-pig iliac artery.

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