Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Subgroups of patients with irritable bowel syndrome (IBS) are likely to respond differently to existing and evolving therapies. The following criteria for subgrouping may be considered: (1) Patients with different predominant bowel habits respond differently to treatment (antidepressants, 5HT3-antagonists, psychotherapy). (2) Postprandial exacerbation of pain or other gastrointestinal symptoms is seen in approximately half of patients with IBS and may identify patients who are more responsive to some classes of drugs (e.g., those targeted at motility). (3) Women appear to respond differently from men to 5HT3-antagonists, and there may be gender differences in gastrointestinal physiology. (4) There is more overlap in the diagnosis of functional dyspepsia and IBS than would be predicted by chance, and both are associated with hyperalgesia to intraluminal distention.
 ...
PMID:Patient subgroups in irritable bowel syndrome that can be defined by symptom evaluation and physical examination. 1058 71

Minimally invasive therapy aims to minimize the trauma of any interventional process but still achieve a satisfactory therapeutic result. The development of "critical pathways," rapid mobilization and early feeding have contributed towards the goal of shorter hospital stay. This concept has been extended to include laparoscopic cholecystectomy and hernia repair. Reports have been published confirming the safety of same day discharge for the majority of patients. However, we would caution against overenthusiastic ambulatory laparoscopic cholecystectomy on the rational but unproven assumption that early discharge will lead to occasional delays in diagnosis and management of postoperative complications. Intraoperative complications of laparoscopic surgery are mostly due to traumatic injuries sustained during blind trocar insertion and physiologic changes associated with patient positioning and pneumoperitoneum creation. General anesthesia and controlled ventilation comprise the accepted anesthetic technique to reduce the increase in PaCO2. Investigators have recently documented the cardiorespiratory compromise associated with upper abdominal laparoscopic surgery, and particular emphasis is placed on careful perioperative monitoring of ASA III-IV patients during insufflation. Setting limits on the inflationary pressure is advised in these patients. Anesthesiologists must maintain a high index of suspicion for complications such as gas embolism, extraperitoneal insufflation and surgical emphysema, pneumothorax and pneumomediastinum. Postoperative nausea and vomiting are among the most common and distressing symptoms after laparoscopic surgery. A highly potent and selective 5-HT3 receptor antagonist, ondansetron, has proven to be an effective oral and IV prophylaxis against postoperative emesis in preliminary studies. Opioids remain an important component of the anesthesia technique, although the introduction of newer potent NSAIDs may diminish their use. A preoperative multimodal analgesic regimen involving skin infiltration with local anesthesia. NSAIDs to attenuate peripheral pain and opioids for central pain may reduce postoperative discomfort and expedite patient recovery/discharge. There is no conclusive evidence to demonstrate clinically significant effects of nitrous oxide on surgical conditions during laparoscopic cholecystectomy or on the incidence of postoperative emesis. Laparoscopic cholecystectomy has proven to be a major advance in the treatment of patients with symptomatic gallbladder disease.
 ...
PMID:Anesthetic implications of laparoscopic surgery. 1060 86

The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.
 ...
PMID:Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain. 1102 33

The observed effects on the symptoms of fibromyalgia of daily oral administration of 5 mg of the 5-HT3 receptor antagonist, tropisetron, for 10 days, could be maintained or exceeded with intravenous administration of only 2 mg of the formulation. Following a single i.v. injection of 2 mg tropisetron, a more rapid and profound reduction in pain was achieved than with 5 mg oral tropisetron per day. In individual cases, patients who had previously experienced no reduction in pain from 10 days of 5 mg oral tropisetron daily responded to i.v. therapy. A more favourable and persistent effect on pain, combined with a simultaneous significant improvement in various vegetative and functional symptoms was achieved with five days treatment with 2 mg tropisetron i.v. per day. The results outlined and the possibility for rapid improvements with drug treatment of fibromyalgia should be confirmed in randomised, placebo controlled trials.
 ...
PMID:Results of the intravenous administration of tropisetron in fibromyalgia patients. 1102 34

In a pilot study, the action of the 5-HT3 receptor antagonist, tropisetron, on different types of local rheumatic pain and inflammatory effects was studied. With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron. The effect of the 5-HT3 receptor antagonists is probable primarily to limit the release of substance P, which acts as a pain and inflammatory mediator, and is itself released by the neurogenic inflammation that occurs after the binding of serotonin to its corresponding receptor. These results should be backed up with placebo controlled studies, which if confirmed, might imply that 5-HT3 receptor antagonists could supplement or replace the local administration of corticosteroids.
 ...
PMID:The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechanism of action of these agents in fibromyalgia? 1102 36

Two young women with chronic nausea and vertigo caused by multiple sclerosis responded to the introduction and maintenance of the 5HT3 receptor antagonist, ondansetron. Palliative care is a neglected aspect of management of degenerative neurological diseases and these cases highlight the approaches that may be used to manage difficult symptoms in the population with multiple sclerosis.
J Pain Symptom Manage 2000 Nov
PMID:Ondansetron in multiple sclerosis. 1106 60

The aim of this study was to investigate if the 5-HT3 antagonist granisetron reduces temporomandibular joint (TMJ) pain in patients with systemic inflammatory joint disorders. Sixteen patients with systemic inflammatory joint disease with pain localized over the TMJ region and tenderness to digital palpation of the TMJ were included. The current resting pain (VASRest) and the pain during maximum mouth opening (VAS(MVM)) of the TMJs were assessed with a 100 mm visual analogue scale. An electronic pressure algometer was used to estimate the pressure pain threshold (PPT) over the lateral aspect of the TMJ. Venous blood was collected for measurement of the plasma and serum levels of 5-HT, erythrocyte sedimentation rate, rheumatoid factor and C-reactive protein. The selective 5-HT3 receptor antagonist granisetron or saline were injected into the posterior part of the upper TMJ compartment in a randomized double-blind manner. The patients in the granisetron group had lower VASRest than the patients in the saline group after 10 min. In the granisetron group, VASRest was decreased after 10 min, while VAS(MVM) was decreased and PPT increased after 20 min. In the saline group, VAS(MVM) was decreased after 20 min. In conclusion, granisetron has an immediate, short-lasting and specific pain reducing effect in TMJ inflammatory arthritis. The 5-HT3 receptor may therefore be involved in the mediation of TMJ pain in systemic inflammatory joint disorders.
 ...
PMID:Immediate effects of the serotonin antagonist granisetron on temporomandibular joint pain in patients with systemic inflammatory disorders. 1119 56

Distal gastric distension may contribute to meal-related dyspeptic symptoms. This study's aims were to determine the effects of distinct nutrient classes on symptoms induced by distal gastric distension and their dependence on 5-hydroxytryptamine(3) (5-HT3) receptors. Nine healthy subjects rated pain, nausea, and bloating induced by isobaric distal gastric distensions (6-24 mmHg) during duodenal lipid, carbohydrate, protein, or saline perfusion after treatment with placebo or the 5-HT3 receptor antagonist granisetron (10 microg/kg iv). Distensions produced greater pain, nausea, and bloating with lipid at 1.5 kcal/min compared with saline (P < or = 0.02), primarily because of greater distal gastric volumes at each distending pressure. In contrast, carbohydrate and protein had no significant effect. At 3 kcal/min, lipid increased symptoms through a volume-independent as well as a volume-dependent effect. Granisetron did not affect symptom perception or gastric pressure-volume relationships. In conclusion, isobaric distal gastric distension produces more intense symptoms during duodenal lipid compared with saline perfusion. Symptom perception during distal gastric distension is unaffected by 5-HT3 receptor antagonism.
 ...
PMID:Effects of nutrients and serotonin 5-HT3 antagonism on symptoms evoked by distal gastric distension in humans. 1120 41

Although the past few years have seen an exponential growth of compounds of potential interest for the treatment of functional gastrointestinal (GI) tract disorders, the gap that still exists between basic and clinical research is easily noticed if one considers the relative paucity of drugs that have received marketing authorisation for the treatment of irritable bowel syndrome (IBS). Traditional efficacy outcomes in drug development for IBS include the ability of the compound to affect GI tract motility (i.e. to exert a prokinetic or an antispasmodic effect), which is thought to be of importance if a motor disorder is the underlying pathophysiological mechanism. More recently, altered visceral sensitivity to a distending stimulus has been suggested to be a key pathophysiological feature, at least in some patients, and has become a target for therapeutic interventions. However, there is now growing consensus that the primary outcome measure in the treatment of functional disorders are those that reflect overall control of the patient's symptoms (pain, diarrhoea, constipation) in everyday situations such as the clinical global improvement scales. Although, in general, guidelines on the design of treatment trials for functional GI tract disorders advise against subcategorisation of patients according to the main symptom (because of symptom instability), subcategorisation indeed makes sense especially in IBS (constipation- or diarrhoea-predominant). Compounds with a specific indication for each subpopulation of patients are now emerging. The rationale for investigations on serotonin (5-hydroxytryptamine; 5-HT) receptor ligands in IBS rests mainly on the fact that serotonin, which may be released by enterochromaffin-like cells in the GI tract as well as from other sources, has a number of well documented motor effects on the GI tract and can produce hyperalgesia in several experimental models. Serotonin receptors belonging to the 5-HT3 and 5-HT4 subtype are the most extensively studied in gastroenterology, although hitherto 'orphan' receptor subtypes, such as the 5-HT7 and the 5-HT(1B/D) receptors, are now emerging. Among 5-HT3 receptor antagonists, alosetron was recently approved for the treatment of diarrhoea-predominant IBS and is an example of a compound that, at least theoretically, may act at multiple levels: by inhibiting visceral sensitivity, by increasing compliance, and by inhibiting excitatory 5-HT3 receptors located on both ascending and descending neuronal pathways involved in peristalsis. For this reason, 5-HT3 receptor antagonists may slow transit, hence the specific indication of alosetron in diarrhoea-predominant IBS. However, alosetron has been recently withdrawn by the manufacturer because of safety concerns. Hypomotility remains an attractive therapeutic target in IBS and the new generation of prokinetics includes several partial agonists at the 5-HT4 receptor, such as tegaserod (HTF-919) and prucalopride (R0-93877). In addition, preliminary evidence suggests that 5-HT4 receptors may also be involved in the modulation of visceral sensitivity. Second-generation 5-HT4 receptor agonists seem to be devoid of the QT-prolonging effects observed in some clinical circumstances with cisapride and may be more active at the colonic level. Piboserod (SB-207266A) is a 5-HT4 receptor antagonist under development for the treatment of diarrhoea-predominant IBS. Finally, interest in 5-HT7 and 5-HT(1B/D) receptor subtypes stems from the observation that the former receptors mediate smooth muscle relaxation (at least in the human colon), whereas sumatriptan (a 5-HT(1B/D) receptor agonist) can affect GI tract motility and visceral sensitivity.
 ...
PMID:Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. 1129 43

Irritable bowel syndrome (IBS) is a functional gut disorder the diagnosis of which is based on clinical symptoms as set forth by the Rome criteria. As the population ages, especially with the population of patients >75 years of age expanding greatly over the next 10 years, IBS is becoming one of the most common diseases of the elderly. Thus far, developing treatment strategies for patients with IBS has been difficult because of the lack of pharmacological targets and the wide range of symptomatology. Additionally, demonstration of a therapeutic benefit is difficult in the presence of a high placebo response observed regardless of the therapy employed. Fibre, antidiarrhoeals and antispasmodics all play some role in the symptomatic treatment of IBS. With the evolution of IBS as a disorder of visceral hypersensitivity, new drugs have been developed that target the enteric nervous system. Tricyclic antidepressants (TCAs) have been found to target the enteric neurons and play a role in pain modulation. Currently, the TCAs are recommended only for severe cases of IBS pain. The newest class of drugs to be approved for use in IBS are the serotonin (5-hydroxytryptamine; 5-HT) antagonists. Specifically, the 5-HT3 receptor antagonists have been shown to decrease symptoms in female patients with IBS. A related class of drugs, the 5-HT4 receptor agonists, is being developed for the treatment of constipation-predominant IBS. Further investigation into the role of spinal afferent neurons in visceral hypersensitivity is at the forefront of IBS research. Several experimental drug therapies for IBS are also discussed in this review including N-methyl-D-aspartate receptor antagonists, neurokinin-1 receptor antagonists, octreotide, clonidine and the selective M3 receptor antagonist, zamifenacin.
 ...
PMID:Drug treatment options for irritable bowel syndrome: managing for success. 1130 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>