tropisetron and Pruritus

Three patients, two females aged 45 and 56 years with metastasized breast carcinoma and one man aged 88 years with inoperable bronchial carcinoma, suffered from severe pruritus. This was only alleviated after treatment with paroxetine, a serotonin re-uptake inhibitor, or with tropisetron, a serotonin antagonist. The youngest woman then could be given chemotherapy, after which clinical recovery occurred, the other patients died, one week and 3 months, respectively, after start of the treatment. Pruritus is a relatively rare symptom in malignancies, but may be worse than pain. In the development and transmission of pruritus signals, in cholestatic icterus as well, serotonin appears to play a more important part than histamine.

Topics: Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma, Bronchogenic; Cholestasis; Diagnosis, Differential; Fatal Outcome; Female; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Paroxetine; Pruritus; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Treatment Outcome; Tropisetron

Our current knowledge about the pathophysiology of pruritus (itch) is summarized. Special concern is given to the hypotheses to explain itch due to cholestatic liver diseases (bile acids, generation of hepatic and intestinal pruritogens, endogenous opioids). Drugs used for the treatment of cholestatic itch are discussed in detail. On the basis of successful treatment of cholestatic itch with 5-hydroxytryptamine (serotonin) subtype-3 receptor antagonists the role of serotonin in nociception is discussed.

Topics: Adult; Child; Cholestasis, Intrahepatic; Female; Humans; Indoles; Male; Nociceptors; Ondansetron; Pregnancy; Pruritus; Receptors, Serotonin; Serotonin Antagonists; Tropisetron

Although intraspinal morphine has been shown to be effective in providing analgesia after cesarean delivery, pruritus as a side-effect remains a common cause of dissatisfaction. The role of ondansetron has been studied in preventing pruritus but the results have been contradictory.. We randomized 98 parturients undergoing elective cesarean section using combined spinal-epidural anesthesia into a double-blinded trial to receive tropisetron 5 mg (T group) or ondansetron 8 mg (O group) or placebo (NaCl group) after delivery, when intrathecal morphine 160 microg and fentanyl 15 microg were used for post-operative pain control. The patients additionally received ketoprofen 300 mg per day. Post-operative itching, nausea and vomiting, sedation and need for rescue analgesics were registered every 3 h up to 24 h, and all patients were interviewed on the first post-operative day.. Seventy-six percent of the parturients in the placebo group, 87% in the ondansetron, and 79% in the tropisetron group had itching. The incidence of post-operative nausea and vomiting was 21%, 20% and 11% of the patients in the placebo, ondansetron and tropisetron groups, respectively. Medication for pruritus was needed by 31%, 23% and 39% of the patients in the placebo, ondansetron and tropisetron groups, respectively. In the post-operative questionnaire, the patients reported less post-operative nausea in the tropisetron group than in the placebo group (P < 0.01).. Neither ondansetron nor tropisetron prevent itching caused by intrathecal morphine with fentanyl. However, tropisetron reduced post-operative nausea.

Topics: Adult; Analgesics, Opioid; Anesthesia, Epidural; Anesthesia, Spinal; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Cesarean Section; Double-Blind Method; Elective Surgical Procedures; Female; Fentanyl; Humans; Indoles; Injections, Spinal; Ketoprofen; Morphine; Ondansetron; Pain, Postoperative; Postoperative Nausea and Vomiting; Pregnancy; Prospective Studies; Pruritus; Time Factors; Treatment Outcome; Tropisetron

Pruritus is the most distressing symptom in haemodialysis (HD) patients. Its aetiology has not yet been delineated, and thus there are no good therapeutical options. Case reports and series attribute antipruritic potency to the serotonin receptor antagonists of the 5-HT3 type in renal pruritus. It was the aim of this study to investigate the antipruritic effect of two different 5-HT3 receptor antagonists and an antihistamine in 11 patients undergoing HD. Pruritus was induced by iontophoresis with serotonin and histamine and recorded before and after HD. These data were compared to those obtained after oral pretreatment with the 5-HT3 receptor antagonists tropisetron 5 mg and ondansetron 8 mg and the antihistamine cetirizine 10 mg. Ten healthy volunteers served as a control group. Vasocutaneous parameters (wheal and flare), skin temperature and alloknesis were also determined. Itching in HD patients and controls was not significantly diminished by oral pretreatment with the serotonin receptor antagonists. In controls, but not in HD patients, cetirizine significantly reduced itching, skin temperature and vasocutaneous parameters. Our data additionally demonstrate that there are no significant differences in vasocutaneous parameters, itching and alloknesis in HD patients before and after dialysis. We conclude that 5-HT3 receptor blockers such as tropisetron and ondansetron and the antihistamine cetirizine do not sufficiently reduce serotonin- and histamine-induced itching in haemodialyis patients.

Topics: Adult; Aged; Antipruritics; Cetirizine; Female; Histamine; Histamine H1 Antagonists; Humans; Indoles; Iontophoresis; Male; Middle Aged; Ondansetron; Pruritus; Reflex; Renal Dialysis; Renal Insufficiency; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Skin; Skin Temperature; Treatment Outcome; Tropisetron

Elevated plasma histamine levels are considered to play a part in the pathophysiology of hemodialysis-related pruritus. However, antihistaminic therapy often fails to provide sufficient relief. Elevated serotonin levels in patients on dialysis therapy have also been described but the effects of 5-HT3 receptor antagonists on hemodialysis-related pruritus remain controversial.. we conducted a study to determine plasma histamine and serotonin levels before and after treatment with 5-HT3 receptor antagonists (tropisetron 5 mg and ondansetron 8 mg) and an antihistamine (cetirizine 10 mg). Eleven hemodialysis patients with a history of pruritus participated in this study,10 healthy volunteers served as control group.. Histamine and serotonin values were normal in patients and controls. Treatment with cetirizine did not significantly reduce histamine levels in patients or in controls. Tropisetron and ondansetron likewise did not alter serotonin levels in patients. Tropisetron treatment did not significantly change serotonin levels in controls.. Histamine and serotonin are no major mediators of pruritus in hemodialysis patients. Elevated histamine levels are occassionally seen and may be due to the increased mast cell number found in a subgroup of hemodialysis patients. Our findings explain the only marginal relief of antihistamines and the controversial antipruritic effect of serotonin receptor antagonists in hemodialysis-related pruritus.

Topics: Adult; Cetirizine; Female; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Indoles; Male; Middle Aged; Ondansetron; Pruritus; Renal Dialysis; Renal Insufficiency; Serotonin; Serotonin Antagonists; Treatment Outcome; Tropisetron

Serotonin (5-hydroxytryptamine, 5-HT) acts as a pruritogen in humans and animals, but the mechanisms of action through that serotonin induces itch response have not been extensively discovered. In our study, we attempted to investigate the role of 5-HT3 receptors in scratching behavior due to intradermal serotonin injection. Intradermal injection of serotonin (14.1-235 nmol/site) into the nape of the neck of mice was performed to elicit itch. Scratching behavior was evaluated by measuring the number of bouts during 60 min after injection. We evaluated the effect of intraperitoneal pretreatment with ondansetron and tropisetron (0.1, 0.3, and 1 mg/kg) on itch induced by serotonin. Also, intradermal ondansetron and tropisetron at doses 50, 100, and 200 nmol/site were concurrently administrated with serotonin. Serotonin produced a significant enhancement in scratching at dose 141 nmol/site. Concurrent administration of ondansetron (50, 100, and 200 nmol/site) and tropisetron (100 and 200 nmol/site) with serotonin reduced scratching activity compared to the animals that only received serotonin. Also, pretreatment with intraperitoneal ondansetron and tropisetron (0.3 and 1 mg/kg) 30 min before serotonin attenuated the itch response. We showed that the scratching induced by intradermal serotonin is mediated by 5-HT3 receptors subtype. It can be concluded that 5-HT3 may play a role in mediating serotonin-associated itch responses, and we introduce 5-HT3 receptors as possible targets for antipruritic agents.

Topics: Animals; Antipruritics; Behavior, Animal; Disease Models, Animal; Dose-Response Relationship, Drug; Indoles; Male; Mice; Ondansetron; Pruritus; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Signal Transduction; Tropisetron

The background of this study is that 5-HT3 receptor antagonists are reported to have an antipruritic effect in uremic and cholestatic pruritus. Recently, we could not confirm such an effect in healthy subjects under experimental conditions. Therefore, it was the aim of the present study to further evaluate a possible antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) on serotonin- and histamine-induced itch before and after skin mast cell depletion in 10 healthy subjects. The results were compared to serotonin and histamine iontophoresis in non-pretreated and pretreated skin with an orally applied antihistamine (cetirizine). Skin mast cell depletion was performed by iontophoretical application of compound 48/80. Wheals and flares were planimetrically evaluated. Itching and burning sensations were rated on an analog scale over a 24-min period. The test protocol also comprised alloknesis, defined as induction of perifocal itch sensations by a mechanical stimulus. When serotonin was iontophoretically applied after mast cells had been depleted before, oral tropisetron resulted not only in significantly lower whealing, itching and alloknesis but also reduced flares. In contrast, after oral pretreatment with tropisetron histamine-induced reactions before and after mast cell depletion did not significantly change. Our study demonstrates that in this model, tropisetron as a 5-HT3 receptor antagonist does not effect histamine-induced itch but has a measurable effect in serotonin-induced reactions when mast cells were depleted before. From these data evidence now exists why tropisetron is to some extent effective in certain types of pruritus such as uremic pruritus, known for increased histamine liberation and increased serotonin levels as well as degranulated and diffusely spread mast cells in the skin.

Topics: Adult; Antipruritics; Cell Count; Female; Histamine; Humans; Indoles; Male; Mast Cells; p-Methoxy-N-methylphenethylamine; Pruritus; Sensation; Serotonin; Serotonin Antagonists; Skin Temperature; Tropisetron

Serotonin type 3 (5-HT3) receptor antagonists have been reported to be a novel therapeutic principle for the treatment of cholestatic and uremic pruritus.. To determine the antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) on histamine and serotonin-induced itch under experimental conditions in comparison to native skin and after pretreatment with an orally applied antihistamine (cetirizine).. Histamine and serotonin were iontophoretically applied in 10 healthy volunteers. Wheals and flares were planimetrically evaluated. Itching and burning sensations were entered on a scale over 24 min. The examination also comprised alloknesis, elicitation of perifocal itch sensation by usually non-itching (e.g. mechanical) stimuli.. Tropisetron did not have any significant influence on histamine-induced reactions but could significantly reduce serotonin-induced flares. Cetirizine led to a significant reduction of all histamine-induced parameters and abolished serotonin-induced wheals.. Serotonin has an own pruritic potency and does not only act over histamine containing mast cells. The antipruritic effect of tropisetron reported in cholestatic and uremic pruritus could not be verified in healthy persons under experimental conditions.

Topics: Adult; Cetirizine; Female; Histamine; Histamine H1 Antagonists; Humans; Indoles; Iontophoresis; Male; Pruritus; Serotonin; Serotonin Antagonists; Skin Temperature; Tropisetron