Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016053 (fibromyalgia)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In more than 40% of patients with fibromyalgia a marked influence on the pain in the skeletal system with a decrease of the tenderness at "tenderpoints" can be achieved by blocking the 5-HT3-receptors with ondansetron or tropisetron-hydrochloride. Physical complaints and vegetative signs also improve. It is discussed if patients not responding to therapy with ondansetron or tropisetron-hydrochloride have to be discriminated as a subgroup of fibromyalgia. More investigations are needed to confirm the described effects.
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PMID:[Therapy of generalized tendomyopathy (fibromyalgia) caused by blocking 5-HT3 receptors]. 787 5

5-HT3-receptor antagonists are potent and highly selective competitive inhibitors of the 5-HT3-receptor with negligible affinity for other receptors. They are rapidly absorbed and penetrate the blood-brain barrier easily. 5-HT3-receptor antagonists are metabolized by diverse subtypes of the cytochrome P450-system, metabolites are excreted mainly in urine. Half-lifes in healthy subjects vary from 3-4 hours (ondansetron, granisetron) to 7-10 hours (tropisetron, hydrodolasetron). 5-HT3-receptor antagonists do not modify any aspect of normal behaviour in animals or induce remarkable changes of physiological functions in healthy subjects. They are well tolerated over wide dose ranges, most common side effects in clinical use are headache and obstipation. Clinical efficacy was first established in chemotherapy-induced emesis. In this indication, 5-HT3-receptor antagonists set a new standard regarding efficacy and tolerability. Further established indications are radiotherapy-induced and post-operative emesis. Antiemetic efficacy results from a simultaneous action at peripheral and central 5-HT3-receptors. Other peripheral actions include reduction of secretion and diarrhea caused by increased intestinal serotonin content (e.g. in carcinoid syndrome), a limited antiarrhythmic activity and a reduction of experimentally induced pain. CNS effects comprise anxiolysis, attenuation of age-associated memory impairment, reduction of alcohol consumption in moderate alcohol abuse and an antipsychotic effect in patients with parkinson psychosis. In migraine, 5-HT3-receptor antagonists show moderate efficacy, as well. Repeatedly demonstrated efficacy of 5-HT3-receptor antagonists in patients suffering from fibromyalgia raises the question for the mechanism of action involved. Ligand binding at the 5-HT3-receptor causes manifold effects on other neurotransmitter and neuropeptide systems. In particular, 5-HT3-receptor antagonists diminish serotonin-induced release of substance P from C-fibers and prevent unmasking of NK2-receptors in the presence of serotonin. These observations possibly provide an approach for the causal explanation of favourable treatment results with 5-HT3-receptor antagonists in fibromyalgia.
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PMID:Preclinical and clinical pharmacology of the 5-HT3 receptor antagonists. 1102 30

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.
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PMID:Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain. 1102 33

From the findings outlined below, there are no reliable predictors of the therapeutic effect of the 5-HT3-receptor antagonists in fibromyalgia. Neither clinical change in pain and vegetative symptoms, nor alterations in biochemical parameters are appropriate predictors of response. The accompanying psychological changes in the form of depressive disorders appear to be somewhat predictive of decreased therapeutic effect, if such definitive statements can be applied to individual cases. If, following new trials, it becomes possible to judge the response of patients to therapy after 3-5 days treatment with 2 mg intravenous tropisetron then predictors will be unnecessary in practice.
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PMID:Do predictors exist for the therapeutic effect of 5-HT3 receptor antagonists in fibromyalgia? 1102 35

We investigated the efficacy and tolerability of short-term treatment with tropisetron, a selective, competitive 5-HT3-receptor antagonist in fibromyalgia. The trial was designed as a prospective, multicenter, double-blind, parallel-group, dose-finding study. We randomly assigned 418 patients suffering from primary fibromyalgia to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily for 10 days. Clinical response was measured by changes in pain score, visual analog scale, tender point count and ancillary symptoms. Responders were prospectively defined as patients showing a 35% or higher reduction in pain score. Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) than placebo (26.2%) (p < 0.05). In the visual analog scale, the group administered 5 mg tropisetron showed a significant improvement (p < 0.05) and the group administered 10 mg tropisetron showed a nonsignificant clinical benefit. The number of painful tender points was significantly reduced (p = 0.002) in the 5 mg tropisetron group. Regarding ancillary symptoms, the 5 mg tropisetron group showed a significant improvement (p < 0.05) in sleep and dizziness. The patients' overall assessment of efficacy was significantly higher for 5 mg (p = 0.016) and 10 mg (p = 0.002) tropisetron than for placebo. The safety and tolerability of tropisetron was good; gastrointestinal tract symptoms were the most frequently reported adverse events. Short-term treatment of fibromyalgia patients with 5 mg tropisetron for 10 days proved to be efficacious and well tolerated. In this study a bell-shaped dose-response curve was seen.
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PMID:Short-term treatment of primary fibromyalgia with the 5-HT3-receptor antagonist tropisetron. Results of a randomized, double-blind, placebo-controlled multicenter trial in 418 patients. 1170 70

As described elsewhere the oral administration of 5 mg of the 5-HT3-receptor-antagonist Tropisetron in fibromyalgia exhibited less amelioration of pain in patients with a depression in comparison to patients without depression. Since an intravenous treatment seems to increase the effect of Tropisetron, the question arises whether patients with depression profit from the intravenous therapy. Methods 68 out patients with fibromyalgia according to ACR-criteria were enrolled in the study. The patients filled in a VAS pain and the Beck Depression Inventory (BDI) before and after a bolus i.v. injection of 5 mg Tropisetron for 5 days [Beck AT, Steer Ra. Beck-Depression-Inventory (BDI) In: Hautzinger M (Hrsg der dt. Ausg.). Testhandbuch. 1. Auflage Bern: Verlag Hans Huber, 1994]. In the beginning the patients had to have > or = 40 mm in the VAS pain from 0-100 mm. The patients were divided into three groups: group 1 = patients with a BDI<19 without experience with antidepressive drugs (n=26); group 2=patients with a BDI > or = 19 (n=22) and negative experience with antidepressive substances, and group 3=patients with a BDI > or = 19 and an accompanying antidepressant drug therapy and some benefit under this therapy (n=20). Results Before the therapy there was no significant difference in VAS pain in the groups, but in BDI there was a significant difference between group 1 (BDI mean value 11.5) in comparison to group 2 (BDI mean value 26.1) and group 3 (BDI mean value 24.8). After therapy all three groups had a significant amelioration of pain: group 1: p=0.000023; group 2: p=0.00073; group 3: p=0.0145. There was a significant difference between the group with BDI<19 and the group with antidepressant drug in amelioration of pain (p=0.044). A significant correlation was found in group 2 with Beck > or = 19 between amelioration of pain and BDI after therapy (p=0.008, r=0.666). In this group a pain-reactive depression and in group 3 an endogenous depression must be discussed.
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PMID:[The influence of depression on the effect of Tropisetron in the therapy of fibromyalgia]. 1262 2

The 5-HT3 receptor is a ligand-gated cation channel located in the central and peripheral nervous system; it has also been detected on a variety of other cells. In the periphery, it is found on autonomic neurons and on neurons of the sensory and enteric nervous system. In the CNS, the 5-HT3 receptor has been localized in the area postrema, nucleus tractus solitarii, nucleus vaudatus, nucleus accumbens, amygdala, hippocampus, entorhinal, frontal, cingulate cortex, and in the dorsal horn ganglia. Further extraneuronal locations include among others lymphocytes, monocytes, and foetal tissue. 5-HT3 receptors modulate the release of neurotransmitters and neuropeptides like dopamine, cholecystokinin, acetylcholine, GABA, substance P, and serotonin itself. They have been demonstrated to be involved in sensory transmission, regulation of autonomic functions, integration of the vomiting reflex, pain processing and control of anxiety. While the physiologic functions of the 5-HT3 receptor are discrete and difficult to detect, it plays a key role in certain pathologic situations related to increased serotonin release. Clinical development of 5-HT3 receptor antagonists revealed a remarkable range of activities. 5-HT3 receptor antagonists do not modify any aspect of normal behaviour in animals or induce pronounced changes of physiological functions in healthy subjects. Clinical efficacy was shown for various forms of emesis like chemotherapy-induced, radiotherapy-induced, and postoperative emesis, diarrhoea-predominant irritable bowel syndrome, anxiety, chronic fatigue syndrome, alcohol abuse, and in pain syndromes such as fibromyalgia and migraine. Most recent data also suggest that 5-HT3 receptor antagonists are effective for the treatment of other rheumatic diseases such as rheumatoid arthritis, tendinopathies, periarthropathies, and myofascial pain. Other possible indications under discussion are chronic heart pain and bulimia. Unfortunately, experimental findings do not yet provide a homogenous conception of the significance of 5-HT3 receptors in all investigated fields; in nociception, for example, contradictory observations are still inadequately explained and complicated by bell-shaped dose-response curves. Further elucidation and better understanding of the serotonergic neuronal network remains a task for the next decade.
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PMID:Physiology and pathophysiology of the 5-HT3 receptor. 1551 4

Several 5-HT3 receptor antagonists are available (tropisetron, ondansetron, granisetron, dolasetron, and palonsetron), and further compounds are in clinical development. These substances show only minor differences in the activity profile regarding their affinity for particular receptors. 5-HT3 receptor antagonists are primarily used and found effective in the prevention and treatment of chemotherapy-induced nausea and emesis, and in postoperative nausea and vomiting (PONV). Antagonism of the 5-HT3 receptors in the peripheral and central nervous system is a probable mechanism of action. The substances are suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting. 5-HT3 receptor antagonists are an important constituent in the prevention and treatment of emesis and nausea caused by radiation therapy, especially in patients receiving whole body or upper abdominal treatment. Alosetron was found clinically effective in diarrhoea-predominant irritable bowel syndrome, whereas tropisetron in fibromyalgia and related pain disorders. Further indications for such treatment include anxiety disorders, alcohol dependence, drug withdrawal, and psychosis related to treatment of Parkinson's disease. 5-HT3 receptor antagonists are well tolerated with the most frequently reported adverse effects being headache, constipation, dizziness, tiredness, and gastrointestinal disturbances such as abdominal pain or constipation. Intravenous administration of serotonin induces the Bezold-Jarisch reflex and causes small reversible changes in electrocardiogram (ECG) parameters.
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PMID:Spectrum of use and tolerability of 5-HT3 receptor antagonists. 1551 6

Current research suggests an involvement of 5-HT3 receptors in peripheral and central perception and processing of pain as well as in inflammation. Tropisetron and other selective 5-HT3 receptor antagonists have been used successfully for pain reduction and treatment of related symptoms in patients diagnosed with fibromyalgia. This article proposes a concept of the underlying pathophysiology and mechanisms of action of 5-HT3 receptor antagonists in the context of the relevant clinical data on their application in patients with rheumatic disease.
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PMID:Analgesic effects of 5-HT3 receptor antagonists. 1551 7

In vitro studies have shown that a blockade of 5-HT3 receptors brings about a reduction of tumor necrosis factor, IL-1 beta, IL-2, IL-6 as well as a decrease in prostaglandins. Clinical trials have provided evidence of pain reduction in a subgroup of fibromyalgia syndrome and, moreover, have demonstrated that tropisetron injected locally for insertion tendinoses and myofascial syndromes with associated trigger points leads to an alleviation of pain that is comparable to injections with the combination of corticosteroids and local anesthetics. The effects achieved by intra-articular injections in cases of osteoarthritis and rheumatoid arthritis paralleled those exerted by intraarticular injection of corticosteroids. In addition, the positive effects produced by systemically administered tropisetron on scleroderma need to be considered since they suggest that this therapeutic principle can also be applied systemically in immunologic processes.
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PMID:New treatment options using 5-HT3 receptor antagonists in rheumatic diseases. 1701 73


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