Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that opening of cephalic arteriovenous anastomoses may be involved in the headache phase of migraine. Indeed, a number of acutely acting anti-migraine drugs, including the ergot alkaloids and sumatriptan, constrict porcine carotid arteriovenous anastomoses. In this study, using pentobarbital anaesthetised pigs, we investigated the effects of eletriptan, a close structural analogue of sumatriptan, on the distribution of common carotid artery blood flow into arteriovenous anastomotic and nutrient (capillary) fractions. Eletriptan (10, 30, 100, 300 and 1000 microg kg(-1), i.v.) decreased the total carotid blood flow, exclusively by decreasing cephalic arteriovenous anastomotic blood flow; nutrient blood flow, particularly to the ear, skin and fat, was significantly increased. The doses of eletriptan needed to reduce arteriovenous anastomotic blood flow and conductance by 50% (ED50) were, respectively, 117+/-21 microg kg(-1) (251+/-45 nmol kg(-1)) and 184+/-42 microg kg(-1) (396+/-91 nmol kg(-1)); the highest dose caused reductions of 84+/-3% and 77+/-4%, respectively. The eletriptan-induced changes in carotid haemodynamics were clearly attenuated by pretreating the pigs with the selective 5-HT1B/1D receptor antagonist GR127935 (0.5 mg kg(-1)). On the basis of these results, we conclude that (1) the eletriptan-induced constriction of cephalic arteriovenous anastomoses as well as the arteriolar dilatation in head tissues is predominantly mediated by 5-HT1B/1D receptors, and (2) eletriptan should be effective in aborting migraine headache. Clinical studies have already demonstrated its therapeutic action in migraine patients.
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PMID:Porcine carotid vascular effects of eletriptan (UK-116,044): a new 5-HT1B/1D receptor agonist with anti-migraine activity. 975 7

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.
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PMID:Pharmacology and efficacy of eletriptan for the treatment of migraine attacks. 1122 Dec 81

The recent clinical development of a number of migraine specific 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and zolmitriptan display both increased stability to first pass metabolic inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to > 120-fold more than sumatriptan), leading to increased oral bioavailability (2- to 5-fold more than the 14% reported for oral sumatriptan). Central penetration and increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or less compared with 50-300 mg doses of sumatriptan) and reduced peripheral exposure to the coronary vasoconstrictor (5-HT1B) receptor. The notable exception being eletriptan, where an active P-glycoprotein blood-brain barrier efflux system effectively negates these benefits and requires an 80 mg oral dose. Differences in the metabolic balance between hepatic P450 (especially CYP 1A2) and MAO-A inactivation lead to potential drug interactions for all TELs with the oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with increased triptan levels). An important but complex MAO-A interaction between a metabolite of propranolol and rizatriptan mandates dosage reduction (to 5 mg) for rizatriptan in the presence of propranolol treatment. There is also an absolute contraindication for the concurrent administration of the MAO-A inhibitor moclobemide and rizatriptan. All the new-marketed TELs have potential clinical benefits and were well-tolerated relative to sumatriptan. Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5 mg) demonstrate at least equivalent efficacy to sumatriptan 25, 50 and 100 mg, respectively, making them suitable first line agents for moderate or severe migraine headaches. Rizatriptan has the fastest onset of effect of the TELs. Naratriptan would appear to have lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for headaches of long duration and with a tendency to recur naratriptan may be the most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and clinical profiles of the TELs facilitates the selection of a triptan which allows optimisation of the clinical benefits for individual patients, minimising the risk of drug interactions and a minimally effective dose to reduce potential adverse events (AEs).
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PMID:Migraine pharmacotherapy with oral triptans: a rational approach to clinical management. 1124 25

Eletriptan (Relpax, Pfizer) is one of a group of anti-migraine medications commonly referred to as 'triptans'. It is a potent serotonin agonist at the 5-HT(1B/1D) receptor and is indicated for the acute treatment of migraine headaches. Eletriptan is administered orally. It is rapidly absorbed and has a bioavailability of 50% compared to 14% for sumatriptan. The relatively high lipophilicity of eletriptan compared to sumatriptan may explain its faster oral absorption and shorter time to onset of action. Results from comparative studies between oral eletriptan and sumatriptan indicate that eletriptan 80 mg was superior to sumatriptan 100 mg in onset of action, headache response rate, pain free response rate and relief of associated migraine symptoms at the 1 or 2 h time intervals. Although there was a modest increase in adverse events with eletriptan 80 mg than with sumatriptan 100 mg, eletriptan received a high patient acceptability rating (84%).
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PMID:Eletriptan. 1177 92

The 5-HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of eletriptan and 2 tablets of Cafergot were compared in a double-blind, randomised, placebo-controlled, parallel-group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4-point scale (3 = severe pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated patients (33%; p < 0.001) reported headache response (improvement from moderate-to-severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p < or = 0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated.
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PMID:Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double-blind, placebo-controlled comparison. 1184 98

The efficacy, safety and tolerability of the 5-HT1B/D receptor agonist eletriptan (40 mg and 80 mg) in acute treatment of migraine was evaluated in a multinational, randomized, double-blind, parallel-group, placebo-controlled, three-attack study treating 1153 patients. In the initial attack, significantly more eletriptan patients reported headache relief and complete pain relief at 2 h vs. placebo (40 mg 62% and 32%, 80 mg 65% and 34%, placebo 19% and 3%; P < 0.0001). Headache relief occurred faster after eletriptan, with more patients at both doses reporting relief 30 min (P < 0.01) and 1 h (P < 0.0001) after treatment than after placebo. There was a significantly lower recurrence rate with eletriptan 80 mg compared with placebo (P < 0.01). Adverse events for all treatments were generally mild or moderate and self-limiting. Eletriptan 40 mg and eletriptan 80 mg both appear to be effective and well-tolerated acute migraine treatments.
Cephalalgia 2002 Feb
PMID:Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo-controlled study across three attacks. 1199 10

This prospective multicentre, double-blind, randomized, parallel-group, placebo-controlled trial evaluated the efficacy and safety of a single dose of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs. A total of 402 adult Japanese migraineurs were diagnosed using International Headache Society (IHS) criteria. At 2 h after a single dose, the headache response rates of eletriptan 20 mg, 40 mg, 80 mg and placebo were 64%, 67%, 76% and 51%, respectively, with all doses significantly superior to placebo (P<0.05). Eletriptan had a statistically significant dose response for headache relief and pain-free response at 2 h post-dose (P=0.0011 and P=0.0291, respectively). Most all-causality adverse events were mild and there were no deaths or discontinuations. Saliva samples were used to assess serum eletriptan levels 2 h post-dose. Pharmacokinetic evaluations showed no clinically significant differences between Japanese and Western subjects. Eletriptan was shown to be efficacious, safe, and well tolerated in Japanese migraineurs.
Cephalalgia 2002 Jul
PMID:Efficacy and safety of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs. 1213 40

Triptans, beginning with sumatriptan, have revolutionized the treatment of migraine. New triptans in several formulations will soon become available in the United States. Although the similarities of these 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists outweigh their differences, important differences in pharmacokinetics and clinical responses do exist. Subcutaneous sumatriptan has the most rapid onset of action and greatest efficacy but the most adverse effects. Intranasal sumatriptan also has rapid onset of action, but at 2 hours its efficacy is comparable to that of oral zolmitriptan. Of the oral triptans, rizatriptan seems to have the greatest early efficacy. Both rizatriptan and zolmitriptan are now available as rapidly dissolving wafers. Almotriptan, the newest of the triptans, has a response rate similar to that of oral sumatriptan and may produce fewer adverse effects. Naratriptan and frovatriptan, with their slow onset, high tolerability, and long half-lives, may have a role in aborting prolonged migraine attacks and in headache prevention. Eletriptan at higher doses (80 mg) has a response rate approaching that of rizatriptan but may be limited by potential side effects. The many triptans available offer the opportunity to individualize migraine treatment, depending on the patient's attack characteristics, tolerance, and preferences.
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PMID:Comparative aspects of triptans in treating migraine. 1273 16

Eletriptan is a member of the triptan family of selective serotonin receptor agonists. These act against migraine by inducing vasoconstriction of the meningeal arteries. In pharmacological tests, eletriptan has shown high affinity for the 5-HT(1B/1D) receptors, which have been implicated in the etiology of migraine headache attacks. Pharmacokinetic evaluations have concluded that eletriptan offers greater bioavailability than sumatriptan, the effective predecessor to eletriptan. A rapid onset of action has also been characteristic of eletriptan in clinical trials, which have likewise demonstrated eletriptan's superiority to sumatriptan in granting relief of headache pain and other symptoms associated with migraine to a greater number of migraine patients. The drug has generally been well tolerated with only mild to moderate adverse events reported. These characteristics make eletriptan an attractive alternative to sumatriptan in the treatment of migraine. (c) 2001 Prous Science. All rights reserved.
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PMID:Migraine headache treatment with eletriptan, a second-generation serotonin receptor agonist. 1278 88

To determine the tolerability and efficacy of eletriptan in patients who had discontinued oral sumatriptan due to lack of efficacy or intolerable adverse events (AEs) during previous clinical treatment (not a controlled trial). Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel group, placebo-controlled multicentre study, patients with and without aura (n = 446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n = 171) or placebo (n = 87) for treatment of up to three migraine attacks. Two-hour headache response, based on first-dose, first-attack data, was 59% for eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was rapid, with 1-h headache response rates significantly superior for E40 and E80 vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly superior to placebo, based on first-dose, first-attack data, for 2-h pain-free response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated significant consistency of response, with headache relief rates at 2 h on at least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs were mild to moderate in severity and dose related. The most commonly reported AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce an effective response in patients who had previously discontinued treatment with sumatriptan due to lack of efficacy or side-effects.
Cephalalgia 2003 Jul
PMID:Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan. 1280 26


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