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)

Nausea and vomiting are typical side effects of cytotoxic therapy and some surgical procedures. These symptoms can represent a major therapeutic challenge and, if inadequately controlled by antiemetic treatment, will result in increased mortality, morbidity, and health care costs. However, the management of nausea and vomiting has improved greatly in recent years following the introduction of the 5-HT3-receptor antagonists, known as 'setrons.' In light of recent developments in antiemetic care, including the approval of the first neurokinin-1-receptor antagonist aprepitant (Emend; Merck and Company, Inc.; West Point, PA) and a new 5-HT3 receptor antagonist palonosetron (Aloxi; MGI Pharma; Minneapolis, MN), this article provides an update on the clinical experience gained with the 5-HT3-receptor antagonist granisetron (Kytril; Roche Laboratories, Inc.; Nutley, NJ) for the management of chemotherapy-induced, radiation-induced, and postoperative nausea and vomiting, and also reviews its use in special patient populations. Granisetron is a potent and highly selective 5-HT3-receptor antagonist that has little or no affinity for other receptors, a characteristic that is thought to underlie the favorable side-effect and safety profiles of this agent. Extensive clinical trial data have shown granisetron to be an effective and well-tolerated agent for the treatment of nausea and vomiting in the oncology and surgical settings. Granisetron has also been shown to be effective and well tolerated in special populations, such as patients refractory to antiemetic treatment, patients with hepatic or renal impairment, and children. Data also suggest that its safety profile and minimal potential for drug-drug interactions would make it an antiemetic agent of choice for elderly cancer patients.
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PMID:Granisetron: an update on its clinical use in the management of nausea and vomiting. 1556 11

Chemotherapy-induced nausea and vomiting (CINV) remains an important and common toxicity of cancer treatment. Recent guideline revisions have classified chemotherapeutic agents into four categories of emesis risk without the use of preventive agents: high (> 90%), moderate (30%--90%), low (10%-30%), and minimal (< 10%). Currently available antiemetic agents, including corticosteroids, 5-hydroxytryptamine (HT)3 receptor antagonists, and neurokinin (NK)-1 antagonists are used alone or in combination depending on the level of emetogenic potential as prophylaxis against the development of CINVduring the acute period (up to 24 hours after chemotherapy) and the delayed period (up to 5 days after treatment). Newer agents, including the second-generation 5-HT3 receptor antagonist palonosetron (Aloxi) and the NK-1 antagonist aprepitant (Emend), offer additional clinical benefit in highly and moderately emetogenic therapy. However, delayed nausea and vomiting continue to occur frequently in many patients and have an impact on quality of life. Other classes of agents including the benzodiazepines and cannabinoids offer the potential for additional protective benefit. Continued research with new drugs and combinations is necessary to meet this significant unmet need of cancer patients.
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PMID:Chemotherapy-induced nausea and vomiting: which antiemetic for which therapy? 1771 96

Palonosetron hydrochloride is a longer-acting selective 5-HT3 receptor antagonist that has been approved for the prevention of chemotherapy-induced nausea and vomiting and is being evaluated for the prevention of postoperative nausea and vomiting. The objective of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 50 mcg/mL when mixed with any of the neuromuscular blocking drugs cisatracurium besylate 0.5 mg/mL, rocuronium bromide 1 mg/mL, succinylcholine chloride 2 mg/mL, and vecuronium bromide 1 mg/mL during simulated Y-site administration. Triplicate samples of palonosetron hydrochloride with each of the neuromuscular blocking drugs were tested. Samples were stored and evaluated for up to 4 hours at room temperature. Physical stability was assessed by turbidimetric and particulate measurements and visual inspection. Chemical stability was assessed by high-performnace liquid chromatography. All of the admixtures were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in all of the samples tested. Palonosetron hydrochloride is physically and chemically stable with cisatracurium besylate, rocuronium bromide, succinylcholine chloride, or vecuronium bromide at the concentrations tested during simulated Y-site administration over 4 hours at ambient room temperature.
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PMID:Compatibility and stability of palonosetron hydrochloride with four neruomuscular blocking agents during simulated y-site administration. 2396 8

Palonosetron hydrochloride is a relatively long-acting selective 5-HT3 receptor antagonist that has been approved for the prevention of chemotherapy-induced nausea and vomiting and is being evaluated for the prevention of postoperative nausea and vomiting. The objective of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 50 mcg/mL when mixed with gentamicin sulfate 5 mg/mL, metronidazole 5 mg/mL, or vancomycin hydrochloride 5 mg/mL during simulated Y-site administration. Duplicate samples of palonosetron hydrochloride with each of the anti-infectives were tested. Samples were stored and evaluated for up to 4 hours at room temperature. Physical stability was assessed by turbidimetric and particulate measurements and visual inspection. Chemical stability was assessed by high-performance liquid chromatography. All of the admixtures were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in all of the samples tesed. Palonosetron hydrochloride is physically and chemically stable with gentamicin sulfate, metronidazole, or vancomycin hydrochloride at the concentrations tested during simulated Y-site administration over 4 hours at ambient room temperature.
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PMID:Compatibility and stability of palonosetron hydrochloride with gentamicin, metronidazole, or vancomycin during simulated y-site administration. 2396 11

Palonosetron hydrochloride is a longer-acting, selective 5-HT3 receptor antagonist that has been approved for the prevention of chemotherapy-induced nausea and vomiting ad is being evaluated for the prevention of postoperative nausea and vomiting. The objective of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 50mcg/mL when mixed with Lactated Ringer's injection, 6% hetastarch in lactated electrolyte injection, or 15% mannitol injection during simulated Y-site administration. Duplicate samples of each admixture were tested. The samples were stored and evaluated for 4 hours at room temperature. Physical stability was assessed by turbidimetric and particulate measurements, and by visual inspection. Chemical stability was assessed by using high-performance liquid chromatography. All of the admixtures were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the observation period. Palonosetron hydrochloride concentration was unchanged in any of the samples throughout the study period. Palonosetron hydrochlorie is physically and chemically stable with Lactated Ringer's injection, 6% hetastarch in lactated elecrolyte injection, or 15% mannitol injection during simulated Y-site administration over 4 hours at ambient room temperature.
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PMID:Compatibility and Stability of Palonosetron Hydrochloride with Lactated Ringer's Hetastarch in Lactated Electrolyte, and Mannitol Injections During Simulated Y-Site Administration. 2396 72

Palonosetron hydrochloride is a longer-acting, selective 5-HT3 receptor antagonist that has been approved for prevention of chemotherapy-induced nausea and vomiting and is being evaluated for prevention of postoperative nause and vomiting. The objective of this study was to evaluate the physical and chemical stablity of palonosetron hydrochloride 50 mcg/mL when mixed with undiluted propofol 1% during simulated Y-site administation. Duplicate samples of this mixture were tested. Samples were stored and evaluated for up to 4 hours at room temperature. Physical stability was assessed by visual inspection. Chemical stability was assessed by high-performance liquid chromatographic analysis. All of the admixtures were opaque white when viewed in normal fluorescent room light and when viewed with a Tyndall beam. After centrifugation, no evidence of precipitation was found. The drug concentrations were essentially unchanged in all of the samples throughout the study. Palonosetron hydrochloride is physically and chemically stable when mixed with propofol as undiluted injections during simulated Y-site administration over 4 hours at ambient room temperature.
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PMID:Compatibility and stability of palonosetron hydrochloride and propofol during simulated y-site administration. 2396 67

Palonosetron hydrochloride is a relatively long-acting selective 5-HT3 receptor antagonist that has been approved for the prevention of chemotherapy-induced nausea and vomiting and is being ealuated for the prevention of postoperative nausea and vomiting. The objective of this study was to evaluate the physical and chemical stability of palonosetron hydrochloride 50 mcg/mL with the B-lactam antibiotics cefazolin sodium 20 mg/mL, cefotetan disodium 20 mg/mL, and the combination ampicillin sodium-sulbactam sodium 20 mg/mL and 10 mg/mL, respectively, during simulated Y-site administration. The effects of each of the antibiotics on palonosetron hydrochloride in these admixtures were tested in triplicate. Samples were stored and evaluated for up to 4 hours at room temperature. Physical stability was assessed by turbidimetric and particulate measurements and visual inspection. Chemical stability was assessed by high-performnace liquid chromatography. All of the admixtures were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study . The drug concentration was unchanged in all of the samples tested. Palonosetron hydrochloride is physically and chemically stable in admixtures with cefazolin sodium, cefotetan disodium and the combination ampicillin sodium-sulbactam sodium at the concentrations tested during simulated Y-site administration over 4 hours at ambient room temperature.
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PMID:Palonosetron hydrochloride compatiblity and stability with three B-lactam anitbiotic during simulated y-site adminstration. 2399 13

Palonosetron (Aloxi) is a potent second generation 5-HT(3) receptor antagonist whose mechanism of action is not yet fully understood. Palonosetron acts at the 5-HT(3) receptor binding site but recent computational studies indicated other possible sites of action in the extracellular domain. To test this hypothesis we mutated a series of residues in the 5-HT3A receptor subunit (Tyr(73), Phe(130), Ser(163), and Asp(165)) and in the 5-HT3B receptor subunit (His(73), Phe(130), Glu(170), and Tyr(143)) that were previously predicted by in silico docking studies to interact with palonosetron. Homomeric (5-HT(3)A) and heteromeric (5-HT(3)AB) receptors were then expressed in HEK293 cells to determine the potency of palonosetron using both fluorimetric and radioligand methods to test function and ligand binding, respectively. The data show that the substitutions have little or no effect on palonosetron inhibition of 5-HT-evoked responses or binding. In contrast, substitutions in the orthosteric binding site abolish palonosetron binding. Overall, the data support a binding site for palonosetron at the classic orthosteric binding pocket between two 5-HT3A receptor subunits but not at allosteric sites previously identified by in silico modelling and docking.
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PMID:Exploring a potential palonosetron allosteric binding site in the 5-HT(3) receptor. 2412 13