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)

Identification of 5-HT receptor subtypes--5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 (possibly A and B), 5-HT3 subtypes, and possibly 5-HT4--has encouraged the manufacture of 5-HT receptor inhibitors with greater subtype specificity. However, it appears that the receptors interact, and drugs initially thought to be specific may have multiple actions. For some conditions such as anxiety/depression, almost all receptors are implicated. Clinical studies provide clear evidence that manipulation of the 5-HT system has a role in treating depression, anxiety, obsessional illness, migraine, and eating disorders. Interactions between the various receptor subtypes make it difficult to identify specific clinical functions. The 5-HT1A receptors may be involved in aggression, anorexia, and hypotension. The 5-HT1B receptors may be involved in aggression, while the 5-HT1C receptors may play a role in central aversion systems and anxiety/depression. The role of the 5-HT1D receptors remains speculative; 5-HT2 receptors appear to be involved in depression, anxiety, appetite, sleep, vasoconstriction, and hypertension. Many drugs that are effective in treating migraine are potent 5-HT2 antagonists. 5-HT3 antagonists at high doses are effective in treating nausea and at low doses in treating anxiety. Treatment of aggression, suicidal behaviour, addiction behaviour, memory impairment, dementia, and schizophrenia with 5-HT inhibitors requires further testing.
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PMID:Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? 269 41

Recent progress in the molecular pharmacology of 5-HT receptors and the development of selective ligands for various 5-HT receptor subtypes has advanced our understanding of the role of 5-HT mechanisms in the control of food intake and bodyweight. The most intensively investigated 5-HT receptor subtypes have been the 5-HT1A receptor, the 5-HT1B receptor and the 5-HT2C receptor. The overall pattern of results to date suggests that selective 5-HT2C agonists may be novel anorectic drugs and prove useful in the treatment of obesity. However, a number of issues remain unresolved, particularly regarding potential side-effects, as the 5-HT2C receptor agonist mCPP has been reported to induce anxiety and nausea in humans, actions that would clearly limit its therapeutic utility. In addition, the possible role of recently cloned 5-HT receptor subtypes such as 5-ht5, 5-ht6 and 5-ht7, remains unexplored and the development of selective ligands for these sites has the potential to lead to new treatments for obesity.
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PMID:Multiple serotonin receptors: opportunities for new treatments for obesity? 869 43

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

Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo (P < 0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the 10-mg dose preferred as it is more effective with a faster onset of action.
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PMID:Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group. 1239 Jun 57

Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting, photo- and phonophobia and malaise. Mild migraine attacks are treated with antiemetics followed by analgesics such as aspirin (acetylsalicylic acid), paracetamol (acetaminophen) or nonsteroidal anti-inflammatory drugs (NSAIDs). Moderate to severe attacks are treated by antiemetics combined with ergotamine or dihydroergotamine. Sumatriptan, a specific serotonin 5-HT1B/D receptor agonist, is used if attacks do not respond to ergotamine or if intolerable adverse effects occur. The new migraine drugs zolmitriptan, naratriptan, rizatriptan and eletriptan differ in their pharmacological profile from sumatriptan, but this translates into only minor differences in efficacy, headache recurrence and adverse effects. Migraine prophylaxis should be implemented when more than 3 attacks occur per month, if attacks do not respond to acute treatment or if the adverse effects of acute treatment are severe. Substances with proven efficacy include the beta-blockers metoprolol and propranolol and the calcium antagonist flunarizine. Drugs less effective or those with unpleasant adverse effects are the serotonin receptor antagonists (pizotifen, methysergide and lisuride), dihydroergotamine, cyclandelate, NSAIDs, valproic acid (sodium valproate) and amitriptyline. The efficacy of aspirin or magnesium is still under evaluation.
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PMID:A practical guide to the management and prevention of migraine. 982 55

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

Good management of migraine requires that the patient participate actively in decisions regarding therapeutic intervention. Most patients, when carefully informed, will engage in a wellness program that includes regular exercise and rest, good nutrition, and avoidance of headache triggers. Acute treatment is probably most likely to be beneficial if it is started early in the migraine attack. Headache severity and associated features, such as nausea, vomiting, or previous treatment responses, can guide selection of medication for acute treatment. Simple analgesics or nonsteroidal anti-inflammatory drugs, with or without antiemetics, are usually the first line of treatment and are effective for some attacks. Combination analgesics or ergotamine preparations represent second-line therapies for patients with infrequent attacks. For patients unlikely to respond to simpler treatments, 5-HT1B/1D receptor agonists or dihydroergotamine offer the best chance for relief. Narcotic analgesics may be needed when other antimigraine drugs prove ineffective, but must be prescribed judiciously. Patients with 3 or more days of headache-related disability per month, or with headaches refractory to acute treatment, are candidates for preventive therapy. Coexisting disease can contribute to decisions on prophylaxis. In many cases, a single agent may be used to treat both migraine and a coexisting disorder. beta-blockers are most often used for preventive therapy. Other options include divalproex, antidepressants, calcium-channel antagonists, serotonin antagonists, and riboflavin.
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PMID:Management of migraine: an algorithmic approach. 1108 19

Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.
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PMID:Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group. 1856 77

Rizatriptan is a novel, selective 5-HT1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46,000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior (P < 0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.
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PMID:Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups. 1128 64

Sumatriptan is a 5-HT1B/D receptor agonist of documented efficacy in relieving migraine and associated symptoms such as nausea and vomiting. In the past decade, several studies reported an important delay of gastric emptying induced by sumatriptan in healthy humans. The impact of this gastric motor effect of sumatriptan in migraineurs is difficult to predict: a further delay in gastric emptying could be detrimental (i.e. increased nausea and epigastric symptoms) in patients already having delayed gastric emptying. However, in patients with functional dyspepsia, sumatriptan is also reported to improve gastric accommodation to a meal and reduce perception of gastric distention, hence relieving epigastric symptoms. Thus, reduced visceral perception could be a mechanism involved in reducing nausea during a migraine attack. Paradoxically, sumatriptan is reported both to relieve the nausea of a migraine attack and to have nausea as a side effect. Although careful analysis of the time of onset of nausea may offer a clue as to the origin of this symptom, available data do not support definite conclusions, all the more so because the gastric motor effect of second-generation triptans are still unexplored. Taken together, the available evidence warrants further studies to clarify the following issues: first, the mechanism responsible for the gastric motor effect of sumatriptan [receptor subtype(s) involved; central vs peripheral mechanism]; secondly, the effects on gastric motility/visceral sensitivity of second-generation triptans (which are 5-HT1B/D receptor agonists) and more recent selective 5-HT1D receptor agonists (proposed as investigational antimigraine agents with less potential to induce coronary vasoconstriction through 5-HT1B receptors); finally, the possible use of drugs improving gastric accommodation to a meal in the management of those dyspeptic patients with impaired fundic relaxation/altered visceral sensitivity.
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PMID:Gastric motor effects of triptans: open questions and future perspectives. 1140 10


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