-
Drugs 1992This review describes clinical experience with tropisetron, a new 5-hydroxytryptamine type 3 (serotonin 3)-receptor antagonist, which was found to possess antiemetic... (Review)
Review
This review describes clinical experience with tropisetron, a new 5-hydroxytryptamine type 3 (serotonin 3)-receptor antagonist, which was found to possess antiemetic properties in animal studies and pilot studies in chemotherapy-treated patients. Tropisetron 5mg once daily is an effective and well tolerated antiemetic treatment for chemotherapy-induced emesis. Tropisetron can be administered without special precautions to all patients who undergo aggressive chemotherapy, and remains effective during multiple chemotherapy courses. The efficacy of tropisetron compares well with that of the best available complicated antiemetic cocktails, but tropisetron is better tolerated. The simple dosage schedule of either 1 injection or 1 capsule per day makes tropisetron ideal for both inpatient and outpatient treatment.
Topics: Animals; Antiemetics; Antineoplastic Agents; Humans; Indoles; Tropisetron; Vomiting
PubMed: 1380428
DOI: 10.2165/00003495-199200433-00005 -
Chinese Clinical Oncology Apr 2020Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA),... (Review)
Review
Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.
Topics: Antineoplastic Agents; Female; Humans; Male; Nausea; Neoplasms; Palonosetron; Tropisetron; Vomiting
PubMed: 31865713
DOI: 10.21037/cco.2019.11.02 -
Drugs Jun 2000Tropisetron is a serotonin (5-hydroxytryptamine; 5-HT) antagonist that is primarily used in the prevention of chemotherapy-induced nausea and vomiting. Antagonism of... (Review)
Review
UNLABELLED
Tropisetron is a serotonin (5-hydroxytryptamine; 5-HT) antagonist that is primarily used in the prevention of chemotherapy-induced nausea and vomiting. Antagonism of 5-HT3 binding sites in the peripheral and central nervous system is the probable mechanism of prevention of acute nausea and vomiting. Effects on delayed nausea and vomiting are less well understood as these are probably not mediated solely by 5-HT3 receptors. Tropisetron monotherapy is effective for the control of acute, and to a lesser extent delayed, nausea and vomiting in patients receiving moderately to severely emetogenic chemotherapy. The combination of dexamethasone and tropisetron is more effective than monotherapy. Complete control of cisplatin-induced nausea and vomiting was obtained in 69 to 97% of patients receiving the combination compared with 46 to 80% receiving tropisetron monotherapy in randomised trials. There were generally no significant differences between the control of acute or delayed nausea and vomiting provided by tropisetron, ondansetron or granisetron in randomised, comparative trials. The antiemetic efficacy of tropisetron was maintained over multiple cycles of chemotherapy. Most comparative studies showed tropisetron monotherapy to be more effective than metoclopramide in controlling acute nausea and vomiting, with the exception of 1 study which showed similar efficacy. However, high dose metoclopramide plus dexamethasone provided similar control of delayed emesis to tropisetron plus dexamethasone. Tropisetron is also effective in children, including those who responded poorly to previous antiemetic treatment. Tropisetron and ondansetron generally have similar efficacies in this population. The drug enhanced patients' quality of life and was well tolerated by adults and children alike. The recommended oral and IV dosage of tropisetron is 5 mg once daily; there is no increase in efficacy with doses >5 mg.
CONCLUSIONS
Tropisetron is similar to other 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting in both adults and children. It is 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.
Topics: Animals; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Indoles; Nausea; Quality of Life; Serotonin Antagonists; Tropisetron; Vomiting
PubMed: 10882164
DOI: 10.2165/00003495-200059060-00008 -
Expert Opinion on Therapeutic Targets Jan 2015Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Despite this, there are no drugs for preventing the onset of AD. Preclinical studies...
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Despite this, there are no drugs for preventing the onset of AD. Preclinical studies suggest that the interaction between amyloid-β peptides (Aβ) and the α7 nicotinic acetylcholine receptor (α7 nAChR) plays a key role in AD pathology, and that α7 nAChR agonists could act as potential therapeutic drugs for AD. A recent study demonstrated that tropisetron, a potent α7 nAChR agonist and serotonin 5-hydroxytryptamine3 receptor antagonist, also bound to the ectodomain of amyloid precursor protein. Furthermore, tropisetron promoted greater improvements in memory than current AD therapeutic drugs, such as memantine and donepezil. Positron emission tomography studies detected Aβ deposition and inflammation in the brains of subjects with amnestic mild cognitive impairment (MCI) before the onset of AD. Given the role of α7 nAChR in Aβ deposition and inflammation, tropisetron represents an attractive potential therapeutic drug to delay or prevent MCI and AD. Additionally as this drug is used internationally to treat chemotherapy-induced emesis, its safety record is already known.
Topics: Alzheimer Disease; Animals; Humans; Indoles; Inflammation; Nicotinic Agonists; Quinuclidines; Serotonin Antagonists; Thiophenes; Tropisetron; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 25399811
DOI: 10.1517/14728222.2014.983901 -
European Journal of Pharmacology Sep 2020Hemorrhagic cystitis is one of the most important complications of cyclophosphamide, a drug widely used in cancer chemotherapy and bone marrow transplantation. 5-HT... (Comparative Study)
Comparative Study
Hemorrhagic cystitis is one of the most important complications of cyclophosphamide, a drug widely used in cancer chemotherapy and bone marrow transplantation. 5-HT antagonists are anti-emetic agents and have been shown to have notable anti-inflammatory and antioxidant properties. This study was designed to investigate the possible protective effects of tropisetron against cyclophosphamide-induced hemorrhagic cystitis in rats. Hemorrhagic cystitis was induced in female rats by cyclophosphamide (270 mg/kg). Tropisetron (2.5, 5 and 7.5 mg/kg), granisetron (2.5 and 5 mg/kg), and ondansetron (5 mg/kg) were injected 15 min before, 4 and 8 h after cyclophosphamide. To evaluate the role of alpha7 nicotinic acetylcholine receptor (α7nAChR), its antagonist, methyllycaconitine (5 mg/kg) was administered 30 min before tropisetron. After 24 h, animals were killed under anesthesia. Macroscopic and histological changes were evaluated. Malondialdehyde (MDA), glutathione (GSH) and Evans blue were measured spectrophotometrically. Furthermore, the protein levels of p38 mitogen-activated protein kinases (P38 MAPK), p-P38, signal transducer and activator of transcription 3 (STAT3), p-STAT3 and Poly (ADP-ribose) polymerase (PARP) were determined using Western blot. Cyclophosphamide administration significantly induced histopathological damages and increased MDA, p-p38/p38, p-STAT3/STAT3, and PARP levels compared with the saline group. Tropisetron treatment diminished histopathological injuries as well as MDA level, and STAT3 activity compared to cyclophosphamide treated rats. Co-administration of methyllycaconitine with tropisetron, partially or completely reversed the protective effects of tropisetron. Our results showed that prophylactic administration of tropisetron markedly ameliorated the cyclophosphamide-induced bladder hemorrhage and inflammation in rats. These effects of tropisetron were α7nAChR dependent.
Topics: Animals; Anti-Inflammatory Agents; Cyclophosphamide; Cystitis; Disease Models, Animal; Female; Granisetron; Hemorrhage; Inflammation Mediators; Lipid Peroxidation; Nicotinic Agonists; Ondansetron; Oxidative Stress; Phosphorylation; Poly(ADP-ribose) Polymerases; Rats, Wistar; STAT3 Transcription Factor; Serotonin 5-HT3 Receptor Antagonists; Signal Transduction; Tropisetron; Urinary Bladder; alpha7 Nicotinic Acetylcholine Receptor; p38 Mitogen-Activated Protein Kinases
PubMed: 32619674
DOI: 10.1016/j.ejphar.2020.173310 -
Behavioural Pharmacology Dec 2020The present study evaluated the acute effects of the 5-HT3 receptor antagonist, tropisetron, on recognition memory in ovariectomized adult female rats. The non-spatial...
The present study evaluated the acute effects of the 5-HT3 receptor antagonist, tropisetron, on recognition memory in ovariectomized adult female rats. The non-spatial novel object recognition task was used to assess recognition memory. In this task, ovariectomized rats explored two identical objects during Trial 1. Immediately after Trial 1, rats were primed either with oil, 250 µg progesterone, 20 µg of estrogen, or 20 µg of estrogen + 250 µg progesterone. Four hours later, the test trial (Trial 2) was initiated. Thirty minutes before Trial 2, rats were injected intraperitoneally with either saline, 1.5 or 2.5 mg/Kg tropisetron. During Trial 2, one arm of the T maze contained an object from Trial 1 (familiar or previously encountered), and a new object (novel) was introduced into the other arm. Exploration times with the novel and familiar objects were recorded and data were converted to percent time spent with the novel object. In oil-primed ovariectomized female rats, treatment with 2.5 mg/Kg tropisetron significantly increased percent time with the novel object. Hormonal-priming with estrogen, progesterone, or estrogen + progesterone did not further accentuate the effects of tropisetron. These results suggest that although tropisetron, estrogen, and progesterone all act as antagonists at the 5-HT3 receptors and blocking 5-HT3 receptors enhances cognition, there appears to be no interaction between tropisetron and these hormones on object recognition.
Topics: Animals; Cognition; Estrogens; Female; Indoles; Memory; Ovariectomy; Progesterone; Rats; Receptors, Serotonin, 5-HT3; Recognition, Psychology; Serotonin 5-HT3 Receptor Antagonists; Tropisetron
PubMed: 32815898
DOI: 10.1097/FBP.0000000000000583 -
The International Journal of... Sep 2019The hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In...
BACKGROUND
The hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In this study, we evaluated the motivation for drug seeking in cocaine self-administering rats exposed to an escalated dosing regimen that endeavored to mimic the characteristic of escalating drug intake in human addicts. Tropisetron is a 5-HT3 receptor antagonist and α7-nicotinic receptor partial agonist. Utilizing rats trained on the escalated-dosing regimen, we examined the effects of tropisetron on control over compulsive drug-seeking behavior that was defined as footshock-resistant lever pressing.
METHODS
Rats were trained to self-administer cocaine with incremental-infusion doses (from 0.6 to 2.4 mg/kg/infusion) across training sessions (3 h/session) or with a long-access paradigm (i.e., 0.6 mg/kg/infusion, 6 h/d training session). The drug-seeking motivations of 2 groups were estimated by the patterns of drug intake and progressive-ratio schedule. The compulsivity for drug seeking of the group with an escalated dose was further evaluated using the footshock-associated seeking-taking chain task.
RESULTS
The rats trained on the dose-escalated protocol achieved the same levels of motivated drug seeking as those subjected to a long-access paradigm, as indicated by cocaine intake per training session and breakpoints on a progressive ratio schedule. Tropisetron attenuated compulsive behavior of rats when pressing of the seeking lever potentially led to footshock. Intriguingly, tropisetron did not change the motivation to seek cocaine when footshock was absent. Tropisetron had no effect on locomotor activities or saccharin self-administration.
CONCLUSIONS
These results demonstrate that tropisetron restored control over compulsive cocaine seeking, and they indicate that 5-HT3/α7-nicotinic receptors may be potential therapeutic targets for relieving compulsive drug seeking.
Topics: Animals; Cocaine; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Electroshock; Male; Rats; Reinforcement Schedule; Self Administration; Tropisetron
PubMed: 31125405
DOI: 10.1093/ijnp/pyz023 -
Drugs Nov 1993Tropisetron is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3) receptor antagonist with antiemetic properties, probably mediated via antagonism of... (Comparative Study)
Comparative Study Review
Tropisetron is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3) receptor antagonist with antiemetic properties, probably mediated via antagonism of receptors both at peripheral sites and in the central nervous system. When compared with antiemetic regimens containing high-dose metoclopramide in a small number of studies, tropisetron was generally as effective at preventing acute and delayed vomiting induced by high-dose cisplatin (> or = 50 mg/m2). In these studies tropisetron completely prevented vomiting occurring in the first 24 hours after chemotherapy in 35 to 76% of patients. Tropisetron was superior to alizapride in preventing emesis induced by high-dose alkylating agents. The effectiveness of tropisetron in patients who had previously had partial control of emesis was improved by the addition of dexamethasone. Tropisetron appears to be well tolerated with the most frequently reported adverse effect being headache. Extrapyramidal effects, which can occur in 5 to 10% of patients receiving high-dose metoclopramide and which may limit its use, have been reported in only isolated cases with tropisetron. Thus, tropisetron is an effective, apparently well tolerated agent which can be administered once daily for the prevention of chemotherapy-induced nausea and vomiting. However, further clinical experience is needed to clarify the optimum role of tropisetron as an antiemetic agent, particularly with regard to other drugs in its class. Nonetheless, preliminary results indicate that tropisetron will be a useful alternative for use in controlling emesis induced by cytotoxic therapy.
Topics: Animals; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Humans; Indoles; Nausea; Neoplasms; Tropisetron; Vomiting
PubMed: 7507039
DOI: 10.2165/00003495-199346050-00009 -
Annals of Oncology : Official Journal... 1993This review discusses the development of tropisetron as an antiemetic drug with the patient in mind. The original aims of the programme and the progress achieved towards... (Review)
Review
This review discusses the development of tropisetron as an antiemetic drug with the patient in mind. The original aims of the programme and the progress achieved towards them to date are described. The efficacy and safety data from two dose-ranging studies and four comparative-treatment studies with tropisetron were combined in a prospectively planned meta-analysis of 799 patients. An integrated safety summary is presented which includes all patients from the six studies. Tropisetron at a dose of 5 mg once daily is an effective and well-tolerated, single-agent, antiemetic treatment, which can be given without special precautions to all patients receiving highly emetogenic chemotherapy. In comparison with metoclopramide, tropisetron is more effective in the prevention of nausea and vomiting. When compared with the most potent cocktail treatments currently in use (containing high-dose metoclopramide, dexamethasone and lorazepam or diphenhydramine), tropisetron is equally effective in the prevention of acute vomiting and somewhat less effective in the prevention of nausea. Overall, tropisetron is an effective and well-tolerated antiemetic treatment that is simple to administer, comparing well with currently available antiemetic cocktails. Tropisetron remains effective for the prevention of nausea and vomiting during multiple chemotherapy courses. The simple dosing schedule (5 mg i.v. day 1; one 5 mg capsule daily, days 2-6) makes tropisetron ideal for both inpatient or outpatient use.
Topics: Antiemetics; Antineoplastic Agents; Humans; Indoles; Nausea; Serotonin Antagonists; Tropisetron; Vomiting
PubMed: 8363994
DOI: 10.1093/annonc/4.suppl_3.s19 -
Archivos Espanoles de Urologia Feb 2023The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been...
OBJECTIVE
The main pathological changes of hemorrhagic cystitis (HC) are bladder inflammation, bladder epithelial damage and mast cell infiltration. Tropisetron has been corroborate to conduct a protective role in HC, but its specific etiology remains unclear. The objective of this research was to estimate the mechanism of action of Tropisetron in haemorrhagic cystitis tissue.
METHODS
Cyclophosphamide (CTX) was utilized to induce the construction of HC rat model, and rats were handled with different doses of Tropisetron. The impact of Tropisetron on the expression of inflammatory factors and oxidative stress factors in the rats with cystitis were measured by western blot, as well as the related proteins of toll-like receptor 4/nuclear transcription factor-κB (TLR-4/NF-κB) and januskinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways.
RESULTS
CTX-induced cystitis in rats was accompanied by notable pathological tissue damage and increased bladder wet weight ratio, elevated mast cell numbers and collagen fibrosis compared to controls. Tropisetron ameliorated CTX-induced injury in a concentration-dependent manner. Futhermore, CTX induced oxidative stress and inflammatory damage, while Tropisetron can alleviate these injuries. Besides, Tropisetron ameliorated CTX-induced cystitis by restraining TLR-4/NF-κB and JAK1/STAT3 signalling pathways.
CONCLUSIONS
Taken together, Tropisetron ameliorates cyclophosphamide-induced haemorrhagic cystitis via modulating TLR-4/NF-κB and JAK1/STAT3 signalling pathways. These findings carry important implication for the study of the molecular mechanisms of pharmacological treatment of hemorrhagic cystitis.
Topics: Animals; Rats; Cyclophosphamide; Cystitis; Hemorrhage; NF-kappa B; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 4; Tropisetron
PubMed: 36914420
DOI: 10.56434/j.arch.esp.urol.20237601.5