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)

Antagonists acting at the 5-hydroxytryptamine3 receptor are potent anti-emetic agents in cases of cytotoxic- and radiation-induced vomiting, and binding sites for these compounds have been described in brainstem areas known to be involved in mediation of nausea and vomiting. We have used autoradiography to examine the distribution of one of these antagonists, [3H]granisetron in the caudal brainstem of the ferret, a commonly used animal model for physiological investigations of emesis. The highest density of binding sites was found to be in the dorsomedial region of the nucleus of the solitary tract, the principal terminus for gastric vagal afferent fibres. Lower levels of binding were observed in the area postrema and the dorsal motor nucleus of the vagus. Following unilateral nodose ganglion excision, displaceable binding of [3H]granisetron in the nucleus of the solitary tract was attenuated on the ipsilateral side by 65%. Bilateral subdiaphragmatic vagotomy abolished binding of [3H]granisetron in the entire dorsal vagal complex. These results provide strong circumstantial evidence that 5-hydroxytryptamine3 receptors are located on vagal afferent terminals in the ferret brainstem.
 ...
PMID:Evidence for presynaptic 5-hydroxytryptamine3 recognition sites on vagal afferent terminals in the brainstem of the ferret. 217 20

Three major areas of medicine are identified in which there is a need for new antiemetic drugs. These are the nausea and vomiting arising from gastrointestinal motility disturbances (functional dyspepsia, diabetic neuropathy, classical migraine), the sickness evoked by abnormal motion, and the severe emesis experienced by cancer patients as a result of certain cytotoxic therapies. For gastrointestinal-related nausea, selective stimulants of gut motility are suggested to form the basis for a new type of antiemetic therapy. In motion sickness, there has been progress in the understanding of the illness, but little advance in the development of new drugs that selectively prevent this type of sickness. In cancer chemo- and radio-therapy, the discovery that selective 5-HT3 (5-HT, 5-hydroxytryptamine) receptor antagonists can prevent severe cytotoxic-evoked emesis now promises to radically change the type of antiemetic therapy given to these patients. This type of antiemetic compound and the pharmacology of the new 5-HT3 receptor antagonists are, therefore, discussed in detail.
 ...
PMID:New antiemetic drugs. 217 55

A total of 28 patients receiving cancer chemotherapy with cisplatin-containing regimens (70-120 mg/m2) participated in an evaluation of the efficacy and safety of GR38032F for the prevention of acute nausea and vomiting. GR38032F, a 5HT3 receptor antagonist, was given 30 min prior to cisplatin as an 8-mg loading dose by i.v. infusion over 15 min, followed by continuous infusion at a rate of 1 mg/h for 24 h. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24 h after cisplatin administration and by an assessment of nausea during the same period. In all, 26 patients were evaluable for efficacy: overall, complete control was achieved in 12 patients (46%), major control (1-2 emetic episodes), in 6 (23%); minor control (3-5 episodes), in 1 (4%); control could not be achieved (failure; greater than 5 episodes) in 7 patients (27%). GR3832F was the tolerated, with no significant drug-related adverse events. These encouraging results should be confirmed in comparative trials.
 ...
PMID:GR38032F, a 5HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting. 252 62

Three main types of 5-HT (serotonin) receptor have been recognised. The 5-HT3 receptor is located on neuronal tissues in the peripheral and central nervous systems. Ondansetron is a highly selective and potent antagonist for this receptor type. The severe nausea and vomiting caused by cytotoxic agents and radiotherapy can be reduced by metoclopramide treatment, but extrapyramidal side effects are common due to antagonism of dopamine receptors. Ondansetron has been found to significantly delay the onset of emesis, and reduce the number of retches and vomits in ferrets receiving cisplatin, cyclophosphamide, or radiation, at much lower doses than metoclopramide and without the associated side effects. Experiments to define the site of action of ondansetron suggest that at least part of its antiemetic action is in the area postrema, though a peripheral site of action in the upper gastrointestinal tract is also a possibility.
 ...
PMID:Pharmacological and anti-emetic properties of ondansetron. 253 94

Ondansetron is a 5-HT3 receptor antagonist which has shown activity in the prevention of nausea and vomiting resulting from cytotoxic therapy. This paper describes the results of studies evaluating the efficacy of oral ondansetron in controlling radiation-induced emesis. Initial non-randomised studies showed that doses of 4 mg q.d.s. or 8 mg t.d.s. of ondansetron achieved complete or major control of vomiting in 77-91% of patients and mild or absence of nausea in 72-77% following single exposure high-dose (8-10 Gy) radiotherapy to the upper abdomen. A subsequent double-blind, prospective, randomised trial compared ondansetron 8 mg t.d.s. with metoclopramide 10 mg t.d.s. in the prevention of emesis following single radiation doses of 8-10 Gy to the upper abdomen. On the day of radiotherapy, ondansetron achieved significantly greater control of vomiting and retching (P less than 0.001) and nausea (P = 0.001) than metoclopramide. An advantage for ondansetron was also seen on days 2 and 3 after irradiation, although this did not reach a statistically significant level. Only two patients, out of 154, in all the studies experienced side effects attributable to ondansetron: one developed headache and the other experienced headache and vertigo. These studies show that ondansetron is a safe drug, with activity in the prevention of radiation-induced emesis and significantly greater efficacy than metoclopramide in the control of nausea and vomiting following single exposure upper abdominal high-dose radiotherapy.
 ...
PMID:Clinical studies with ondansetron in the control of radiation-induced emesis. 253 96

In a phase I study of BRL43694A, a 5HT3-receptor antagonist, a single dose of 40 micrograms/kg was given to 24 patients. All patients received cytostatic treatment expected to cause nausea and vomiting. During the first 24 h, 12 patients were completely protected from nausea and vomiting, 4 experienced nausea and 8 had moderate vomiting; mild headache occurred in 10 patients. No cardiovascular (including ECG) changes took place. Apart from headache, no neurological side effects occurred.
 ...
PMID:A phase I study of a new 5HT3-receptor antagonist, BRL43694A, an agent for the prevention of chemotherapy-induced nausea and vomiting. 254 9

In ferrets, the selective 5-hydroxytryptamine (5-HT) 5-HT3 receptor antagonist BRL 43694 given as a single injection (0.05-0.5 mg kg-1 i.v.) before cisplatin, or by divided dose (2 x 0.005-2 x 0.5 mg kg-1 i.v.) before and after cisplatin dramatically reduced or abolished the severe cisplatin-induced vomiting. BRL 43694 also substantially reduced the vomiting induced by cyclophosphamide:doxorubicin, and prevented the trimelamol-induced emesis. The severe emesis caused by whole body exposure to X-irradiation was prevented by intravenous or oral BRL 43694. A single i.v. dose of BRL 43694 given during an emetic episode or within the peak emetic period, abolished the vomiting induced by the cytotoxic drugs and by X-irradiation, usually within 30 s. Where the induction of emesis was prevented or subsequently abolished by BRL 43694, the associated behaviour (subjectively assessed as nausea) was also absent or greatly attenuated. BRL 43694 (0.1 mg kg-1 i.v.) did not affect the emesis evoked in dogs by the dopamine agonist apomorphine. The potent anti-emetic activity of BRL 43694 is discussed in terms of potential clinical use, and of the fundamental role that 5-HT3 receptors may play in the mechanisms of nausea and vomiting.
 ...
PMID:The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694. 285 11

15 patients receiving cytotoxic drugs (other than cisplatin) that had previously produced nausea and vomiting refractory to first-line antiemetics were given a selective 5-HT3 receptor antagonist (GR38032F), 4 mg intravenously and 4 mg orally, immediately before chemotherapy, the oral dose being repeated 5 and 10 h later. Nausea, vomiting, and side-effects were recorded for the ensuing 24 h. The 15 patients received a total of thirty-one courses of chemotherapy. Only 1 patient vomited. The only adverse events were dryness of the mouth in 1 patient, mild sedation in 1, and diarrhoea in 1, and these were not clearly drug related.
 ...
PMID:Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. 288 54

GR38032F is a highly selective 5HT3-receptor antagonist which inhibits vomiting induced by cisplatin, cyclophosphamide or X-radiation in the ferret. Since cisplatin selectively increased the levels of 5HT and 5HIAA in the intestinal mucosa, a possible site of the antiemetic action of GR38032F may be on 5HT3-receptors on vagal afferents in the small intestine. The potent antiemetic action of GR38032F should be of clinical value in reducing the nausea and vomiting associated with radiotherapy or chemotherapy of cancer.
 ...
PMID:Antiemetic properties of the 5HT3-receptor antagonist, GR38032F. 296 67

The clinical application of 5-HT3 receptor antagonists has enabled continuation of the course of chemotherapy including cisplatin, which induces strong nausea and vomiting, and to prevent the delay of curative treatment for cancer patients receiving neoadjuvant chemotherapy. However, with the development of basic research on the mechanisms of vomiting, each 5-HT3 receptor antagonist has appeared to have different pharmacological actions and, subsequently, the difference in the clinical efficacy of each drug has been reported in Europe and USA. In freshly advanced head and neck carcinoma cases, a randomised crossover study was performed to compare the efficacy and safety profile of a single intravenous dose for 7 days of azasetron (10 mg/day) or granisetron (3 mg/day) in the prophylaxis of nausea and vomiting induced by multi-drug chemotherapy including cisplatin (50 mg/m2 or 60 mg/m2). Anti-emetic effects were evaluated by the protective rates for nausea and vomiting for 7 days following the start of cisplatin administration. Both 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute and delayed emesis induced by chemotherapy, whereas the efficacies of azasetron on day 3 and 4 were superior to those of granisetron. No adverse effect of either drug was observed in this study.
 ...
PMID:[A randomized crossover comparison of azasetron and granisetron in the prophylaxis of emesis induced by chemotherapy including cisplatin]. 748 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>