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)

5-HT3 receptors have been the focus of much research during the last decade. They are characterised by being located on neurones both peripherally and centrally; 5-HT3 agonists cause a rapid depolarisation of the membrane potential which results from the opening of cation channels; the 5-HT3 response rapidly desensitizes. 5-HT3 receptors appear to have a modulatory role on other neurotransmitters. The identification of selective agonists and antagonists for this receptor type has allowed the discovery of several important new therapeutic applications. The use of 5-HT3 receptor antagonists in psychoactive illnesses is being explored clinically. In addition, ondansetron, a selective 5-HT3 receptor antagonist, is already being used to prevent the severe nausea and vomiting caused by cancer chemotherapy and radiotherapy. The pharmacological properties of 5-HT3 antagonists are discussed in this chapter.
 ...
PMID:5-HT3 receptors and the therapeutic potential of 5-HT3 receptor antagonists. 184 Feb 27

Despite a number of significant advances over the past decade, prevention and treatment of chemotherapy-induced emesis remain formidable problems, particularly with cisplatin-containing regimens. Nearly one third of patients receiving high-dose cisplatin still experience substantial emesis despite the best available conventional antiemetics, and the toxic effects of these agents remain quite troublesome. In recent years, a new class of agents, the serotonin antagonists, has been identified. These agents hold promise for clinical utility in a wide range of areas. Selective antagonists of the serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor have proven in early clinical trials to be potent antiemetic agents in patients receiving cytotoxic chemotherapy, with efficacy comparable to or superior to that of conventional antiemetics. Toxic effects to date with the 5-HT3 receptor antagonists have been modest. The current state of knowledge with respect to these agents as antiemetics for patients receiving cytotoxic chemotherapy is summarized.
J Natl Cancer Inst 1991 May 01
PMID:Serotonin antagonists: a new class of antiemetic agents. 185 Aug 6

We conducted a double-blind, randomized crossover study to compare the toxicity and antiemetic efficacy of the 5-hydroxytryptamine3 receptor antagonist batanopride with that of metoclopramide in 21 chemotherapy-naive patients receiving at least 70 mg/m2 cisplatin. The study was terminated when hypotension was observed following the infusion of batanopride at other institutions testing similar drug schedules. Although we observed no hypotension following treatment with batanopride in this trial, we did note asymptomatic prolongation of the corrected QT interval (QTc), PR interval, and QRS complex on the EKG in the batanopride arm. Of 15 evaluable patients, 8 experienced less than or equal to 2 episodes of emesis within 24 h of the first batanopride infusion, whereas 9/15 subjects experienced less than or equal to 2 emetic episodes following the administration of metoclopramide. Overall, the evidence suggests that this dosing schedule for batanopride may be too toxic for clinical use.
Cancer Chemother Pharmacol 1991
PMID:Double-blind, randomized crossover study of metoclopramide and batanopride for prevention of cisplatin-induced emesis. 185 80

Fifty six patients, with histologically confirmed cancer, who received highly emetogenic chemotherapy, were entered on a randomized double blind, low versus high dose, study of granisetron, a 5HT3 receptor antagonist. A single dose of intravenous granisetron protected the majority of patients from nausea and vomiting, 160 micrograms/kg was more effective than 40 micrograms/kg with no more side effects. Additional doses of granisetron conferred added benefit to patients who experienced breakthrough symptoms. Granisetron at a dose range of 40-240 micrograms/kg over a 24 hour period was well tolerated with the only side effect being mild headache.
 ...
PMID:High versus low dose granisetron, a selective 5HT3 antagonist, for the prevention of chemotherapy-induced nausea and vomiting. 196 78

A total of 25 patients (5 groups of 5) were given single i.v. doses of 5, 10, 20, 40 and 60 mg MDL 72,222 (a 5-HT3 receptor antagonist) at 15 minutes before the commencement of a 24-h cisplatin infusion (total dose, 120-200 mg) to determine the efficacy and safety of the former in the prevention of nausea and vomiting associated with such chemotherapy. All patients completed the study. The time to onset of vomiting was significantly correlated with dose. All patients vomited following doses of 5 and 10 mg (range, 1-6 episodes), with onset being noted at 5-8 h. At the 20-mg level, only one episode of vomiting was observed in 3/5 patients, with onset being observed at 18-22 h. Following doses of 40 and 60 mg, 3/10 patients did not vomit; in the remaining patients the number of episodes ranged from 1 to 6, but a significant increase occurred in the time to onset of symptoms. At the higher doses, nausea tended to be milder in nature both at onset and at the time of maximal severity. A similar dose-effect trend was seen in the time to onset of the maximal severity of nausea. The time to and requirement for escape medication was similarly extended at doses of greater than or equal to 20 mg MDL 72,222. Pain at the injection site in one patient was the only unwanted effect associated with MDL 72,222. The results suggest that the i.v. injection of 20 mg MDL 72,222 should be further explored in the control of nausea and vomiting associated with cisplatin administration.
Cancer Chemother Pharmacol 1991
PMID:A single-dose-finding study of the antiemetic effect and associated plasma levels of MDL 72222 in patients receiving cisplatin. 201 17

Recent advances in the understanding of emesis have resulted in the development of serotonin 3 receptor antagonists. The careful use of these drugs and other conventional antiemetic agents can substantially reduce the nausea and vomiting associated with chemotherapy and improve the quality of life for cancer patients undergoing treatment.
 ...
PMID:Management of vomiting associated with cytotoxic therapy. 201 89

Antiemetic effects of serotonin 5-HT3 receptor antagonists (ICS205-930, zacopride, BRL43694, GR38032F) were investigated in Suncus murinus. Veratrine, nicotine, copper sulfate, cisplatin, cyclophosphamide and motion sickness were used as emetic stimuli. Serotonin 5-HT3 receptor antagonists did not inhibit emetic responses to veratrine, nicotine, copper sulfate and motion sickness. However, cisplatin- and cyclophosphamide-induced emesis was strongly blocked by them. Both subcutaneous and intravenous injections of 5-HT3 antagonists were effective. Serotonin 5-HT1 and 5-HT2 receptor antagonists were less effective. These results clearly indicate that a 5-HT3 receptor-mediated mechanism(s) is involved in the emesis caused by cancer chemotherapeutic agents and that 5-HT3 receptor antagonists are very effective as prophylactic drugs.
 ...
PMID:Selective blockade of cytotoxic drug-induced emesis by 5-HT3 receptor antagonists in Suncus murinus. 204 Dec 20

A new group of selective 5HT3 antagonists are proving to be effective anti-emetics for cytotoxic and radiation induced vomiting in both animal models and man. Current anti-emetic regimens often benefit from combination therapy, in particular the efficacy of metoclopramide (which can be a weak 5HT3 antagonist), can be improved by combination with dexamethasone, another anti-emetic. Hence it was of interest to evaluate whether a 5HT3 receptor antagonist GR38032F could be improved by combination with dexamethasone. Vomiting induced by cyclophosphamide in the ferret was observed after pre-treatment with dexamethasone alone or in combination with GR38032F. Animals were also observed for signs of 'nausea'. Dexamethasone alone proved a weak anti-emetic in this system but did have significant effects on 'nausea'. GR38032F has previously been shown to be capable of totally controlling emesis due to cyclophosphamide in the ferret. Here a dose of GR38032F that is not 100% effective was employed; this was shown to have effects on 'nausea' but most interestingly its anti-emetic action was increased by combination with dexamethasone. This may be important for the minority of patients whose vomiting is not completely controlled by GR38032F alone.
Br J Cancer 1990 Jan
PMID:Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret. 213 8

A total of 33 patients with myeloma receiving treatment with high-dose melphalan (140-200 mg/m2 i.v.) were given the 5HT3 antagonist Ondansetron (Glaxo) as an antiemetic. In 42% of patients, emetic episodes were either abolished (15%) or reduced to two or less (27%). Efficacy was not related to scheduling (two regimens) or total dose. No sedative or other significant side effects were seen. Ondansetron is a highly effective non-sedative antiemetic that justifies further assessment in combination with other antiemetics in patients receiving cytotoxic drugs associated with the production of severe nausea and vomiting.
Cancer Chemother Pharmacol 1990
PMID:Ondansetron--a new safe and effective antiemetic in patients receiving high-dose melphalan. 213 64

In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.
 ...
PMID:[Gastrointestinal toxicity induced by anticancer drugs--including new antiemetic drugs]. 214 Apr 98


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