5-HT3 receptor antagonists regulate autonomic cardiac dysfunction in primary fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) frequently presents with autonomic and/or functional symptoms. Tropisetron, a selective serotonin-3 antagonist, is widely used for the treatment of this disease. However, its effects on autonomic function are not well known. In the present study, we evaluated whether tropisetron improved cardiac autonomic symptoms in FMS. Thirty-six patients were treated with physiotherapy and 5 mg tropisetron intravenously for 5 days. An additional 36 patients were treated with physiotherapy alone. Thirty-six volunteers served as healthy controls. The ISAX apparatus was used for spectral analyses of cardiac R-R intervals. High frequencies and mid frequencies were analysed to assess sympathetic and parasympathetic activity. The findings were correlated with pain intensity. ISAX findings were significantly different in FMS patients compared to healthy controls and did not correlate with pain perception. Ten of 12 pathological parameters disappeared during treatment in the tropisetron group. Our results indicate that tropisetron reduced not only pain perception but also had a favourable effect on cardiac dysfunction during treatment.

New treatment options using 5-HT3 receptor antagonists in rheumatic diseases.

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.

The 5-HT3 receptor antagonist tropisetron inhibits T cell activation by targeting the calcineurin pathway.

Tropisetron, an antagonist of serotonin type 3 receptor, has been investigated in chronic inflammatory joint process. Since T cells play a key role in the onset of several inflammatory diseases, we have evaluated the immunosuppressive activity of tropisetron in human T cells, discovering that this compound is a potent inhibitor of early and late events in TCR-mediated T cell activation. Moreover, we found that tropisetron specifically inhibited both IL-2 gene transcription and IL-2 synthesis in stimulated T cells. To further characterize the inhibitory mechanisms of tropisetron at the transcriptional level, we examined the DNA binding and transcriptional activities of NF-(kappa)B, NFAT and AP-1 transcription factors in Jurkat T cells. We found that tropisetron inhibited both the binding to DNA and the transcriptional activity of NFAT and AP-1. We also observed that tropisetron is a potent inhibitor of PMA plus ionomycin-induced NF-(kappa)B activation but in contrast TNF(alpha)-mediated NF-(kappa)B activation was not affected by this antagonist. Finally, overexpression of a constitutively active form of calcineurin indicated that this phosphatase may represent one of the main targets for the inhibitory activity of tropisetron. These findings provide new mechanistic insights into the anti-inflammatory activities of tropisetron, which are probably independent of serotonin receptor signalling and highlight their potential to design novel therapeutic strategies to manage inflammatory diseases.

Treatment of tendopathies with tropisetron.

A comparison between a local anesthetic drug and the 5-hydroxytryptamine 3 (5-HT3) receptor antagonist tropisetron in treating tendopathies or periarthropathies revealed that tropisetron has a longer effect on resting pain and pain on movement than the local anesthetic drug. The most likely explanation for this effect probably is a blocking of stimulated 5-HT3 receptors at the nociceptors in conjunction with an inhibited release of substance P and other neurokines because of this blockage. Further studies will have to show whether the action of tropisetron in tendopathies is as favorable as that of corticosteroids.