Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Migraine is a chronic neurological disorder, characterized by attacks of severe, usually unilateral and throbbing headache accompanied by nausea, vomiting, and photophobia and photophobia. Sometimes transient neurological (aura) symptoms may precede or accompany the headaches. Acute drug therapy comprises nonspecific drugs, including simple analgesics and non-steroidal anti-inflammatory drugs, often in combination with antiemetics, and specific antimigraine drugs, such as ergotamine, dihydroergotamine and sumatriptan. Sumatriptan is a potent and selective serotonin1D receptor agonist, which can be administered orally and via the subcutaneous or intranasal route. The drug is well tolerated and is consistently highly effective in most patients. Significant limitations, however, include the occurrence of chest symptoms, suggestive of cardiac ischaemia; recurrence of the headache within 24 h after initial successful treatment; and in a minority of patients, abuse of sumatriptan with daily 'sumatriptan-dependent headaches'. Administration during the aura phase does not affect the aura itself, but is not recommended because the subsequent headache will not be prevented in that case. Preliminary data of new serotonin1D receptor agonists, such as 311C90 and MK-462 are promising in terms of increased efficacy after oral administration, but side-effect profile and incidence of headache recurrence are similar to those observed after the use of sumatriptan. Intranasal administration of dihydroergotamine may also be effective, but data are very limited.
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PMID:Acute treatment of migraine attacks. 755 Nov 26

311C90 is a novel, centrally and peripherally, acting 5-hydroxytryptamine1D receptor agonist. We investigated the efficacy and safety of 1, 5, and 25 mg of oral 311C90 in the acute treatment of migraine in a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 84 patients. The proportion of patients in whom the headache improved within 2 hours from moderate or severe to mild or no pain (primary efficacy measure) was 15% for placebo-treated patients and 27% (1 mg), 62% (5 mg), and 81% (25 mg) for patients treated with 311C90. Treatment differences compared with placebo were 12% (95% CI - 12, 37; p = 0.460) for 1 mg 311C90, 47% (CI 21, 73; p < 0.005) for 5 mg 311C90, and 66% (CI 43,89; p < 0.001) for 25 mg 311C90. Photophobia and nausea also showed improvement after 311C90. Adverse events were generally mild and transient in all treatment groups. There were no clinically significant changes in ECG recordings, blood pressure, or laboratory tests. Oral 311C90 (5 and 25 mg) is highly effective and well tolerated in the acute treatment of migraine. The response rates and treatment differences compared with placebo in this study suggest possible superiority over existing antimigraine therapies. This needs to be confirmed in formal comparative trials.
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PMID:311C90, a new central and peripherally acting 5-HT1D receptor agonist in the acute oral treatment of migraine: a double-blind, placebo-controlled, dose-range finding study. 861 25

This study investigated the efficacy of zolmitriptan (Zomig, formerly 311C90) in acute migraine therapy. Patients with a history of migraine were randomized in a double-blind, multicenter, placebo-controlled, dose range-finding study of oral zolmitriptan 1, 2.5, 5, or 10 mg versus placebo for the treatment of a severe or moderate migraine headache. Patients with persistent or recurrent headache 4 to 24 hours after the initial dose, who did not take escape medication, were eligible to receive a second blinded dose of either zolmitriptan or placebo. Of 1,144 patients treated, 999 evaluable patients completed the study. The headache response rates with zolmitriptan doses > or = 2.5 mg were 44 to 51% at 1 hour, 65 to 67% at 2 hours, and 75 to 78% at 4 hours (all significantly superior to placebo). Also, zolmitriptan effectively relieved migraine-associated symptoms such as nausea, photophobia and phonophobia, and reduced activity impairment. Rates of headache recurrence, headache persistence, and use of escape medication were lower with zolmitriptan doses > or = 2.5 mg than with placebo. In patients with persistent or recurrent headache, a second zolmitriptan dose effectively treated both headache and nonheadache symptoms. Zolmitriptan was well tolerated, with a lower incidence of adverse events being reported with doses < or = 2.5 mg than with those > or = 5 mg. Zolmitriptan is a well tolerated and effective acute migraine therapy providing rapid relief of migraine headache within 1 hour. A clear dose-response relationship between efficacy and tolerability suggests that 2.5 mg is the optimal initial dose for the acute treatment of a migraine attack.
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PMID:Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. The 017 Clinical Trial Study Group. 937 90

The efficacy of zolmitriptan (Zomig, 311C90), a 5-hydroxytryptamine (5HT)1B/1D receptor agonist, in the acute oral treatment of migraine was evaluated in an extensive clinical trial program. Four randomized, placebo-controlled studies (total 2480 patients) were performed; data from two of these trials established that a 2.5 mg dose was on the shoulder of the dose-response curve (2-h headache response rate 64%), showing similar efficacy to the 5 mg dose (67%). In this program, the efficacy of zolmitriptan was not influenced by the pretreatment headache duration; the presence of aura preceding the headache, migraine associated with menses or migraine upon awakening; or by concomitant use of oral contraceptives or antidepressants. In addition, zolmitriptan 5 mg proved consistently effective in the treatment of multiple migraine attacks for up to 1 year. Zolmitriptan reduced the incidence of nausea, photophobia and phonophobia, reduced impairment of normal activity and demonstrated positive effects on patients' quality of life. Thus, zolmitriptan is a highly effective acute oral antimigraine therapy, with 2.5 mg providing the optimal balance between efficacy and tolerability.
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PMID:Zolmitriptan (Zomig, 311C90), a novel dual central and peripheral 5HT1B/1D agonist: an overview of efficacy. 939 15

Zolmitriptan (Zomig, formerly 311C90) at doses of 0.5-50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses > or = 2.5 mg. In the clinical pharmacology studies, the overall incidence of subject exposures experiencing at least one adverse event was 52% with zolmitriptan 2.5 mg (28% with placebo). In placebo-controlled studies, the overall incidence of patients with at least one adverse event was dose-dependent for zolmitriptan over the 1-15 mg dose range, e.g. 42% and 46% with 1 and 2.5 mg, respectively and 58% with 5 mg (29% with placebo). Only four serious adverse events attributable to zolmitriptan were reported. In a long-term study, during which 2,058 outpatients treated a total of 31,579 migraine attacks with either one or two zolmitriptan 5 mg doses over a period of up to 1 year, the number of attacks associated with at least one adverse event was similar after one (26%) and two (24%) doses. The majority (59%) of the adverse events reported in this study (59%) occurred within 2 h of dosing, were predominantly mild (59%) or moderate (35%) in intensity, of < or = 4 h duration (58%), required no further action (94%). In placebo-controlled studies, the percentage of patients who reported severe adverse events was similar with zolmitriptan 2.5 mg (4%) and placebo (5%). The most frequently reported adverse events with zolmitriptan in the placebo-controlled clinical studies were asthenia, heaviness (other than chest or neck), dry mouth, nausea, dizziness, somnolence, paresthesia and warm sensations. The type and severity of the adverse events was not influenced by gender (although the frequency of reported adverse events was higher in females, as was the case in the placebo group), age, presence of aura prior to the attack, association of migraine with menstruation, concurrent medication, or by the addition of a second zolmitriptan dose. Zolmitriptan showed a similar tolerability profile in the long-term study, in which a low withdrawal rate due to adverse events of 8% was observed. Zolmitriptan was not associated with an increased frequency of central nervous system-related adverse events in a comparative study of sumatriptan, despite pre-clinical and neurophysiological evidence of a dual peripheral and central action of zolmitriptan. Moreover, zolmitriptan doses of 5-20 mg produced no statistically significant effects on objective assessments of psychometric function. Zolmitriptan had no clinically significant effects on blood pressure (even in patients with controlled mild to moderate hypertension or impaired renal function), ECGs (e.g. there was no evidence of ischemic events) or clinical chemistry, hematological or urinalysis measurements. In summary, zolmitriptan is well tolerated, particularly at the recommended dose of 2.5 mg. Zolmitriptan has a well-defined dose-response with 2.5 mg proving highly effective and optimizing the benefit/risk ratio of treatment. Thus, zolmitriptan is well suited as an acute oral treatment for migraine in the outpatient setting.
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PMID:Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on > 3000 subjects treated with zolmitriptan. 939 16

This international open-label study evaluated the tolerability and efficacy of zolmitriptan (Zomig, 311C90), a selective 5-HT1B/1D receptor agonist, in the long-term treatment of multiple migraine attacks. Patients who had previously participated in placebo-controlled zolmitriptan studies were recruited. A total of 2058 patients treated 31,579 migraine attacks (average 15 per patient), for up to 1 year. Twenty-six percent of attacks treated with a single zolmitriptan 5-mg dose were associated with at least one adverse event (24% treated with two doses). The most frequent adverse events included asthenia (14% of patients), nausea (12%), somnolence (10%), dizziness (11%), and paresthesia (11%). The rank order of the most common adverse events was not influenced by sex, age, or number of zolmitriptan doses taken and was similar between attacks 1 and 45. The majority of adverse events (59%) occurred within 2 hours of dosing, were of either mild (59%) or moderate (35%) intensity, of 4 hours' duration or less (67%), and required no further action (94%). Following an initial 5-mg dose of zolmitriptan, the 2-hour headache response rate (reduction in headache pain from moderate or severe before treatment to mild or no pain at 2 hours posttreatment) was 81% in patients treating moderate and severe attacks (19,639 of 24,161). Patients were pain-free at 2 hours in 55% of all attacks (16,510 of 29,808). The efficacy of zolmitriptan was not influenced by age, sex, weight, use of prophylactic antimigraine medication, or association of attacks with menstruation. Analysis of the overall population and a subgroup who treated 30 or more migraine attacks showed that zolmitriptan was consistently effective across attacks. Overall, 67% of patients who treated five or more attacks reported zolmitriptan to be effective in 80% to 100% of attacks. Zolmitriptan produced meaningful migraine relief and improvement in normal activity impairment in 73% and 78% of moderate and severe attacks, respectively. Patients treated recurrence of moderate or severe headache with a second zolmitriptan dose in 32% of attacks which responded to the first dose within 2 hours. Where required, a second zolmitriptan 5-mg dose for treatment of recurrence produced a headache response rate of 90% at 2 hours postdose. Thus, zolmitriptan 5 mg (plus an optional second 5-mg dose for treatment of recurrence) is well tolerated and effective in the acute treatment of multiple migraine attacks over periods up to 1 year.
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PMID:The long-term tolerability and efficacy of oral zolmitriptan (Zomig, 311C90) in the acute treatment of migraine. An international study. The International 311C90 Long-term Study Group. 956 7

Zolmitriptan (previously known as 311C90) is a serotoninergic 5-HT1B/D agonist with high oral bioavailability with a double, central and peripheral, action mechanism. Evaluation of its clinical efficacy was developed in a program of clinical studies (search and confirmation of dosis, comparative and long term studies) and through analysis of efficacy in different clinical situations. Zolmitriptan shows a high effectiveness in the treatment of migraine crisis, significantly reduces the headaches by 2 hours of its administration, reduce the symptoms associated with migraine (nausea, photophobia and phonophobia) and improves the quality of life of the migraine patient. The efficacy is independent of the type of migraine characteristics of the patient as well as of the administration of other concomitant medications. The dosis of 2.5 mg of zolmitriptan has been found to be the optimum considering both efficacy and tolerability.
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PMID:[Clinical efficacy of zolmitriptan in migraine]. 985 91

A bibliographic review of the safety profile of 311C90 or zolmitriptan is performed in the present study showing the large number of clinical trials carried out in both healthy volunteers and patients with migraine. The molecule, a potent, selective agonist for the 5HT1B/1D receptors with central and peripheral activity does not appear to have significant influence on arterial pressure. ECG and Holter ECG studies did not show any alterations in healthy volunteers. In migraine patients, the ECG did not demonstrate ischemic alterations at any of the dosages of zolmitriptan used. In patients who had undertaken treatment for months, the hemogram and biochemical follow up did not show any changes. This new triptan was well tolerated in a wide spectrum of patients and healthy volunteers. Complaints of subjective side effects usually increase according to an increase in dosage. The most frequent adverse effects were nausea and dizziness. Other discomforts are: dryness of the mouth, sensation of heat, paresthesia, asthenia, drowsiness, and dizziness. The sensation of heaviness, tightness or pressure of the throat and chest have also been reported. The adverse effects reported with 5 mg of zolmitriptan are similar to those found with 100 mg of sumatriptan. The adverse side effects are usually mild, last a short time and remit without therapy. Zolmitriptan used together with the other most often used drugs in migraine patients did not show any important clinical interactions. However, it seems reasonable to limit the daily administration of zolmitriptan with monoaminoxidase inhibitors (MAOI-A) since a possible increase of the levels of zolmitriptan and its metabolites may be detected in the presence of one (moclobemide). At a dose of 2.5 mg, zolmitriptan appears to provide the best relationship between benefits and risk.
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PMID:[Safety profile of 311C90 (zolmitriptan)]. 985 92

This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.
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PMID:Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study. 1184 97

Preclinical studies have shown that zolmitriptan is a selective serotonin 5-HT(1B/1D) receptor agonist (triptan). Randomised, placebo-controlled, double-blind trials in patients with migraine have shown that zolmitriptan has good efficacy measured using 2 h response and pain-free rates. Migraine-associated symptoms, including nausea, photophobia and phonophobia, are also improved with zolmitriptan. Oral zolmitriptan (2.5 and 5 mg) has an onset of action within 45 min and efficacy is sustained in most patients who respond at 2 h. The orally-disintegrating zolmitriptan tablet has the advantage that it may be taken immediately, without the need for additional fluids, any time a migraine headache occurs. Patients may benefit in terms of improved efficacy from the convenience of the disintegrating tablet, since there is evidence that taking triptan therapy as early as possible in an attack is advantageous. For similar reasons, as well as improved efficacy, a nasal spray formulation is in development. Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura. There is no tachyphylaxis following repeated doses for multiple attacks of migraine over a prolonged period of time. Compared to placebo, the incidence of persistent migraine headache is reduced by zolmitriptan and recurrent migraine headache occurs less frequently. Zolmitriptan has also shown efficacy in the treatment of persistent and/or recurrent migraine headache. Comparative clinical studies have shown overall that zolmitriptan has similar or superior efficacy to sumatriptan in the treatment of migraine. Specifically, zolmitriptan 2.5 mg was significantly more effective than sumatriptan 25 or 50 mg according to a number of end points, including headache response at 2 h. Oral zolmitriptan is also effective in the acute treatment of cluster headache. Zolmitriptan is generally well tolerated, with most adverse events being mild-to-moderate, transient and resolving without intervention or the need for treatment withdrawal. The consistent efficacy in treating all types of migraine and the choice of available formulations make zolmitriptan acceptable to patients and a suitable first-line therapy for the treatment of migraine.
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PMID:Review of zolmitriptan and its clinical applications in migraine. 1208 98


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