Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Work on the pharmacological effects of high-dose metoclopramide led Beecham scientists to identify the role of 5-HT3 receptors in the emetic response to cytostatic drugs and X-irradiation in animals. Further studies have confirmed and extended knowledge of the novel 5-HT3 antagonist granisetron. Dose-dependent inhibition of the 5-HT-induced Bezold-Jarisch reflex in anaesthetized rats was shown by doses of 0.1-10 micrograms/kg i.v. granisetron. Radioligand binding studies in rat brain revealed a high affinity (Ki 0.26 nM) for 5-HT3 sites and much lower affinities (Ki 1000 - greater than 10,000 nM) for 5-HT1, 5-HT2, 5-HT1A, 5-HT1B/C, 5-HT1C, alpha 1, alpha 2, dopamine D2, benzodiazepine, picrotoxin, beta, histamine H1 or opioid mu, kappa or delta binding sites. Granisetron was effective prophylactically after oral or i.v. doses or by intervention after i.v. doses (0.005-0.5 mg/kg) against cisplatin, cyclophosphamide and doxorubicin or X-irradiation-induced emesis in the conscious ferret in the absence of any side effects. It was concluded therefore, that granisetron is a selective and potent anti-emetic worthy of clinical investigation.
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PMID:The role of specific 5-HT3 receptor antagonism in the control of cytostatic drug-induced emesis. 216 86

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 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

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

5-HT research is now more than 50 years old, and it has generated a wealth of therapeutic agents, some of which have had a major impact on disease management. The 5-HT reuptake inhibitors (SSRIs) are among the most widely prescribed drugs for treating depression and a variety of other disorders including anxiety, social phobia and premenstrual dysphoria (PMD). The other major success stories of 5-HT research are the discovery of 5-HT1B/D receptor agonists for treating migraine and 5-HT3 receptor antagonists for chemotherapy and radiation-induced emesis. The role of 5-HT in the mechanism of action of antipsychotic agents remains a topic of intense research, which promises better treatments for schizophrenia in the future. Compounds interacting with 5-HT1F, 5-HT2C, 5-HT6 and 5-HT7 receptors are currently under investigation and may prove to have important therapeutic applications in the future.
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PMID:The medical benefit of 5-HT research. 1188 47

Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide-ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long-term experience.
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PMID:Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. 1255 71

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.
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PMID:Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan. 1280 26

Depression is a highly debilitating disorder that has been estimated to affect up to 21% of the world population. Despite the advances in the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), there continue to be many unmet clinical needs with respect to both efficacy and side effects. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. There is tremendous diversity in the types of targets and approaches being taken. At one end of a spectrum is combination therapies that maintain the benefits associated with SSRIs but attempt to either improve efficacy or reduce side effects by adding additional mechanisms (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2C, alpha-2A). At the other end of the spectrum are more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis. In between, there are many approaches that range from directly targeting serotonin receptors (5-HT2C, 5-HT6) to targeting the multiplicity of potential mechanisms associated with excitatory (glutamate, NMDA, mGluR2, mGluR5) or inhibitory amino acid systems (GABA) or peptidergic systems (neurokinin 1, corticotropin-releasing factor 1, melanin-concentrating hormone 1, V1b). The present review addresses the most exciting approaches and reviews the localization, neurochemical and behavioral data that provide the supporting rationale for each of these targets or target combinations.
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PMID:Innovative approaches for the development of antidepressant drugs: current and future strategies. 1648 68

Rizatriptan and zolmitriptan are both used to relieve acute migraine and cluster headaches. The mechanism of action is similar to the other triptans, in that they reverse abnormal cerebral vasodilation through their activity as 5-HT1B receptor agonists. Triptan-induced vasoconstriction is attributed to its activity on peripheral 5-HT1B receptors and has rarely been reported to result in stroke, myocardial infarction and ischemic colitis. We present two cases of renal infarction associated with therapeutic triptan use. The first patient is a 57-year-old man with a history of hypertension that was well controlled on valsartan and hydrochlorothiazide. He was recently diagnosed with cluster headaches and was treated with indomethacin, prednisone, butalbital-acetaminophen-caffeine and hydrocodone without relief. He then received two therapeutic doses of rizatriptan on each of the two days prior to presentation. Subsequently, he presented to the emergency department complaining of nausea, vomiting and right-sided abdominal pain. A computerized tomography (CT) scan of the abdomen and pelvis with intravenous contrast revealed a very large wedge shaped infarction of the right kidney. The second patient is a 34-year-old man with a past medical history significant only for life-long migraine headaches successfully treated for the past six years with zolmitriptan. Shortly after taking one therapeutic dose of zolmitriptan, he presented to the emergency department complaining of nausea and left-sided abdominal pain. A CT scan of the abdomen and pelvis with intravenous contrast revealed multiple wedge-shaped infarctions of the left kidney. Renal infarction was confirmed in both patients by arteriogram of the renal arteries. Although both rizatriptan and zolmitriptan are effective in the treatment of migraine and cluster headaches, they may induce peripheral vasospasm leading to renal infarction.
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PMID:Renal infarction during the use of rizatriptan and zolmitriptan: two case reports. 1661 76