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)

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10-30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.
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PMID:Aripiprazole. 1619 61

Healthcare providers believe they have a positive impact on controlling chemotherapy-induced nausea and vomiting (CINV), yet patients still consider CINV to be one of the most distressing side effects of chemotherapy. The effect of CINV on daily activities has been measured using the Functional Living Index-Emesis (FLIE) scale, a validated, nausea- and vomiting-specific, patient-reported outcome instrument comprising nine items in each of two domains. This research explores the potential correlation between reducing CINV and improved quality of life. In clinical trials, patients completed the FLIE questionnaires 24 and 96 hours after receiving moderately emetogenic chemotherapy and antiemetic therapy using a serotonin receptor antagonist (ondansetron, dolasetron, or palonosetron). Significantly more patients given palonosetron had FLIE scores that reflected lessened impact of nausea on daily life during the acute period (0-24 hours) and of nausea/vomiting during both the acute and delayed periods (days 2-4). These findings strongly suggest that better antiemetic prevention allows patients to maintain their functional status for up to 5 days after chemotherapy.
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PMID:Measuring the maintenance of daily life activities using the functional living index-emesis (FLIE) in patients receiving moderately emetogenic chemotherapy. 1644 51

The serotonin receptor type 3 is a pentameric ligand-gated ion channel regulating intestinal motility, nausea, and vomiting in humans. The HTR3B gene codes for the subunit B of this receptor. The HTR3B transcription start site is not unequivocally identified. In the present study we used transcription start site analyses, transcript-specific RT-PCR, and functional promoter analyses to identify the 5' structure of the HTR3B gene. According to these experiments, two alternative promoters control the expression of different HTR3B transcripts in the peripheral and central nervous system. The transcription start sites observed in the intestine corresponded to the current human genome annotation (NCBI Build 36.1, March 2006). The transcription start sites in the brain, however, were localized in a region about 4000 bp downstream. The brain transcripts lacked the coding first exon of the HTR3B structure published earlier but had an upstream-extended exon 2 containing a new potential translational start site. Reporter gene analyses showed significant promoter activity of the genomic region located 1560 bp upstream to 93 bp downstream of the brain-specific transcription start sites. This data suggests a different transcriptional regulation of the HTR3B gene in the peripheral and the central nervous system that leads to the expression of transcripts with variations in the 5' coding sequence. Further studies on the expression, structure and function of therefore expected tissue-specific 5-HT(3B) isoforms are required.
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PMID:Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine. 1701 May 35

Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A) agonists have been proposed as a potential therapeutic strategy for the selective treatment of opioid-induced respiratory depression. We investigated the clinical applicability of this principle in healthy volunteers. Twelve subjects received 0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously (i.v.) over approximately 2 h. At the start of the morphine infusion, they received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or placebo. Respiratory depression (hypercapnic challenge) and pain (electrical stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses applied to the nasal mucosa) were assessed at baseline, at the end of the morphine infusion, and a third time after antagonizing the opioid effects by i.v. administration of 2 mg naloxone. The linear relationship between the minute ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2)) after morphine administration (P<0.001), indicating respiratory depression, which was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co-administration of buspirone had no effect on morphine-induced respiratory depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus 0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant morphine-induced analgesia was observed in both pain models and was reversed by naloxone but unaffected by buspirone. Buspirone significantly increased the nausea induced by morphine (P=0.011). Oral co-administration of a high dose of the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy for opioid-induced respiratory depression. This is indicated by its lack of anti-respiratory depressive effects and by the buspirone-associated increase of morphine-induced nausea.
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PMID:The partial 5-hydroxytryptamine1A receptor agonist buspirone does not antagonize morphine-induced respiratory depression in humans. 1718

Serotonin is an important gastrointestinal signaling molecule. It is a paracrine messenger utilized by enterochromaffin (EC) cells, which function as sensory transducers. Serotonin activates intrinsic and extrinsic primary afferent neurons to, respectively, initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin is also a neurotransmitter utilized by a system of long descending myenteric interneurons. Serotonin is synthesized through the actions of 2 different tryptophan hydroxylases, TpH1 and TpH2, which are found, respectively, in EC cells and neurons. Serotonin is inactivated by the serotonin reuptake transporter (SERT)-mediated uptake into enterocytes or neurons. The presence of many serotonin receptor subtypes enables selective drugs to be designed to therapeutically modulate gastrointestinal motility, secretion, and sensation. Current examples include tegaserod, a 5-HT(4) partial agonist, which has been approved for treatment of irritable bowel syndrome (IBS) with constipation in women and for chronic constipation in men and women. The 5-HT(3) antagonists, granisetron and ondansetron, are useful in combating the nausea associated with cancer chemotherapy, and alosetron is employed in the treatment of IBS with diarrhea. Serotonergic signaling abnormalities have also been putatively implicated in the pathogenesis of functional bowel diseases. Other compounds, for which efficacy has not been rigorously established, but which may have value, include tricyclic antidepressants and serotonin selective reuptake inhibitors to combat IBS, and 5-HT(1) agonists, which enhance gastric accommodation, to treat functional dyspepsia. The initial success encountered with serotonergic agents holds promise for newer and more potent insights and therapies of brain-gut disorders.
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PMID:The serotonin signaling system: from basic understanding to drug development for functional GI disorders. 1724 88

Chemotherapy-induced nausea and vomiting (CINV) is a common and serious problem encountered by many patients receiving anticancer therapy. Up to three fourths of all cancer patients experience chemotherapy-related emesis. Risk factors include specific chemotherapeutic agents used, female gender, age less than 50 years, and history of nausea or vomiting. Since CINV can complicate or prevent administration of planned therapy, decrease quality of life, and increase healthcare costs, its effective management is essential. Although serotonin receptor antagonists have significantly improved outcomes, next-generation analogs such as palonosetron have shown greater specificity and increased efficacy. Novel agents like the neurokinin-1 receptor antagonist aprepitant are also active, particularly when combined with palonosetron and dexamethasone. In recent years, the greatest advances have been made in the prevention of vomiting (especially acute vomiting), although uncontrolled nausea is still a major concern for many patients. Better treatments are needed for management of delayed CINV and for patients who do not respond to standard antiemetic therapies.
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PMID:Chemotherapy-induced nausea and vomiting: clinician and patient perspectives. 1736 28

Gastroparesis is a disorder of gastric emptying that occurs in the absence of mechanical obstruction. Its cardinal features include nausea, vomiting, bloating, early satiety and discomfort. Weight loss, dehydration, electrolyte disturbances and malnutrition may develop in severe cases. The majority of cases is idiopathic, long standing diabetes mellitus is responsible for about 25-30% of cases. Diabetic gastroparesis may render glucose control extremely difficult, its treatment represents a major challenge. Besides frequent, small meals and psychological support, several drug options are available, however, their efficacy is limited and only a few randomized studies have been performed to date. Prokinetic agents (erythromycin, domperidone, metoclopramide) and antiemetics (phenothiazines, serotonin antagonists, butyrophenones) are the most wide-spread medicaments. Among the novel, recently developed agents, 5-HT4 serotonin receptor agonists and dopamine D2 receptor antagonists are the most promising. Injection of botulinum toxin into the pyloric sphincter resulted in faster gastric emptying and symptom alleviation in some studies. Gastric electric stimulation appears to be one of the most effective options, both low and high-frequency stimulation may alleviate symptoms. Gastrostomy/jejunostomy and other surgical interventions are considered as "last resort".
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PMID:[Gastroparesis and its treatment options]. 1829 33

The 5-HT(3) receptor (5-HT(3)R) occupies a special place among the serotonin receptor subtypes because it has been shown to be a ligand-gated ion channel, which is involved in a number of physiological functions and important pathologies. 5-HT(3)R antagonists have shown an outstanding efficacy in the control of the emesis induced by anticancer chemotherapy and few adverse side-effects, so as to revolutionize the treatment of nausea in cancer patients. This review covers the authors' work performed during the past decade in the development of 5-HT(3)R ligands belonging to the class of arylpiperazine derivatives related to quipazine (quipazine-like arylpiperazines, QLAs) and represents the extension of the review previously published in Current Topics in Medicinal Chemistry in 2002. The discussion is focused mainly on the most significant structure-affinity relationships emerged in the progress of the work and shows how the original ideas have evolved in the recent years.
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PMID:The interactions of the 5-HT3 receptor with quipazine-like arylpiperazine ligands: the journey track at the end of the first decade of the third millennium. 2016 48

Nausea and vomiting are relatively common in advanced cancer and is dreaded more than pain by patients. The history, pattern of nausea and vomiting, associated symptoms, and physical examination provides clues as to etiology and may guide therapy. Continuous severe nausea unrelieved by vomiting is usually caused by medications or metabolic abnormalities, while nausea relieved by vomiting or induced by eating is usually due to gastroparesis, gastric outlet obstruction, or small bowel obstruction. Drug choices are empiric or based on etiology. Metoclopramide has the greatest evidence for efficacy followed by phenothiazines and tropisetron. Corticosteroids have not been effective in randomized trials except in the case of bowel obstruction. Treatment of nausea unresponsive to first-line medications involves rotation to medications which bind to multiple receptors (broad-spectrum antiemetics), the addition of another antiemetic to a narrow-spectrum antiemetic (a serotonin receptor antagonist such as tropisetron to a phenothiazine), rotation to a different class of antiemetic (tropisetron for a phenothiazine), or in-class drug rotation. Venting gastrostomy, octreotide, and corticosteroids will reduce nausea and vomiting associated with malignant bowel obstruction.
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PMID:Nausea and vomiting in advanced cancer. 2019 57

We retrospectively examined the results of antiemetic therapy with granisetron and dexamethasone; with granisetron, dexamethasone and aprepitant; and with palonosetron, dexamethasone and aprepitant, in patients who received chemotherapy with cisplatin at 50 mg/m2 or more for the first time. Vomiting was dramatically reduced by the concomitant administration of aprepitant. There was no difference in this effect when palonosetron was used instead of granisetron as a serotonin receptor antagonist. There was also no significant difference in the percentage of patients without nausea among the 3 groups. The results of this study indicate that vomiting in patients receiving chemotherapy can be controlled using aprepitant in combination with two other drugs.
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PMID:[Retrospective analysis of antiemetic effect in patients receiving cisplatin]. 2177 1


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