Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 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

Zolmitriptan is a new serotonergic agonist with excellent oral bioavailability exhibiting a potent symptomatic antimigraine effect. Zolmitriptan is a selective agonist of 5-HT1B/D receptors. 5-HT1B receptors are concentrated in the wall of the cranial extracerebral arteries. 5-HT1D receptors are located on the trigeminal terminals which receive pain from the leptomeningeal vessels. Migraine pain has its origin on cranial vessels. In fact, during a migraine attack the trigeminovascular system, which is composed by the cranial vessels and its trigeminal terminals, is activated. The activation of this system induces both dilatation and aseptic inflammation of cranial vessels. Zolmitriptan blocks both vascular phenomena. Its agonist action upon the 5-HT1D receptor ends the aseptic inflammation by inhibiting the release of vasoactive peptides. The dilatation of meningeal vessels disappears due to the stimulation of zolmitriptan of 5-HT1B receptors. As this drug crosses the blood brain barrier, zolmitriptan has both peripheral and central actions over the espinal trigeminal nucleus, which is rich in 5-HT1B/D receptors. Thus, the mechanism of action of zolmitriptan is double. On the one hand, zolmitriptan acts peripherally inhibiting dilatation and inflammation of cranial vessels. On the other, zolmitriptan exhibits a central nociceptive action in the brainstem nuclei. This dual action of zolmitriptan on migraine pain is completed with its beneficial effects on nausea and vomiting, due to its binding to the nucleus of the tractus solitarius, the center for control of vomiting.
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PMID:[Mechanism of action of zolmitriptan]. 985 90

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

Migraine is a common disabling neurological disorder, associated with headache, nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin 5HT(1B/1D) receptor agonist with a long track record in clinical studies and in the treatment of acute migraine. A nasal formulation has been developed that has clear evidence for local absorption, resulting in plasma drug concentrations within 2 minutes of dosing, central nervous system penetration 3 minutes later, and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing. Intranasal zolmitriptan offers advantages to migraineurs, particularly those seeking a more rapid onset of effect without wishing to self-inject, or those with gastrointestinal upset. The comparison of pharmacokinetic and clinical data available from different formulations of zolmitriptan contributes both to the understanding of its mode of action and the characteristics required of an acute migraine treatment if it is to meet patient needs.
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PMID:Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy. 1641 61