Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 5-HT3 receptor antagonists (ondansetron 0.1 mg kg-1 SC 30 min; bemesetron 0.03 mg kg-1 SC 45 min) on nicotine-induced increases in locomotor activity were measured in male Sprague-Dawley rats. Intermittent daily injections of nicotine (0.3-1.2 mg kg-1 SC 30 min) resulted in increased locomotor activity as measured by photocell counts. The effect of nicotine was not affected by administration of the 5-HT3 receptor antagonists at doses that are reported to block nicotine- and morphine-induced place-preference conditioning. Neither of the 5-HT3 receptor antagonists tested affected activity counts in vehicle treated animals. Nicotine-induced hyperactivity was blocked by the dopamine antagonist haloperidol (0.03 mg kg-1 SC 2 h) and by the nicotinic antagonist mecamylamine (1 mg kg-1 SC 1 min). The effects of a range of doses (0-1 mg kg-1) of the 5-HT3 receptor antagonists ondansetron, bemesetron, granisetron and tropisetron on hyperactivity induced by 0.6 mg kg-1 nicotine were then assessed. Only tropisetron at 1 mg kg-1 attenuated nicotine-induced hyperactivity. To demonstrate the efficacy of the present range of doses of the 5-HT3 receptor antagonists in this study, conditioned taste aversion experiments were conducted. Ondansetron (0.1 mg kg-1) failed to attenuate a conditioned taste aversion to saccharin induced by nicotine (0.6 mg kg-1), but did induce a reduction in saccharin preference in choice tests following three saccharin-ondansetron pairings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats. 765 69

Ondansetron is a selective 5-HT3 receptor antagonist which has previously been reported in the Journal to be a promising new agent for use as prophylaxis against nausea and vomiting caused by chemotherapy and radiotherapy. Since the publication of this original review, further studies have been published that show ondansetron to be an effective antiemetic agent in patients receiving chemotherapy and radiotherapy. Several studies have shown ondansetron to be a more effective antiemetic agent than high-dose metoclopramide in patients with emesis induced by high- and low-dose cisplatin treatment, and noncisplatin chemotherapy-induced emesis. The drug as mono-therapy does not appear to offer any advantage over alternative therapies against delayed high-dose cisplatin-induced nausea and vomiting; however, extremely limited data suggest that ondansetron plus dexamethasone may be useful in this indication. Trials have shown combination therapy with ondansetron and dexamethasone to be significantly more effective than both ondansetron monotherapy and a standard antiemetic regimen comprising metoclopramide, dexamethasone and diphenhydramine against acute high-dose cisplatin-induced emesis. Results from a number of small scale trials suggest that ondansetron may be an effective treatment for chemotherapy-induced emesis refractory to conventional antiemetic therapy. Ondansetron also appears to be more effective against refractory emesis induced by noncisplatin chemotherapy than that induced by cisplatin chemotherapy. Several trials have shown ondansetron to be more effective than placebo as prophylaxis against postoperative nausea and vomiting; a further trial has shown single-dose ondansetron to be significantly more effective than single-dose droperidol or metoclopramide in this indication. In addition, several trials have shown ondansetron to be more effective than placebo as treatment for nausea and vomiting that has commenced postoperatively. The overall incidence of adverse events in ondansetron recipients during chemotherapy-induced emesis studies was 36%. Headache and constipation are the most common adverse events during ondansetron therapy. Thus, recent data affirms the efficacy of ondansetron in the treatment of acute chemotherapy-induced nausea and vomiting and shows it to be especially efficacious when combined with dexamethasone. It appears that the drug will also have a substantial role in the prophylaxis and treatment of postoperative nausea and vomiting.
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PMID:Ondansetron. An update of its therapeutic use in chemotherapy-induced and postoperative nausea and vomiting. 769

Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT3 receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies.
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PMID:[Efficacy of ondansetron in radiation-induced nausea and vomiting: review of the literature]. 770 1

We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT3 receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were distended, with pressure increments of 4 mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale of 0-10. Personality traits were measured using standard psychological methods, and somatic pain was evaluated by immersion of the nondominant hand in cold water. The effect of 5-HT3 antagonism was tested with a single intravenous dose of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel syndrome, but rectal distension was perceived similarly in irritable bowel syndrome and controls. Pain tolerance to cold water was also similar in irritable bowel syndrome and controls. Ondansetron induced rectal relaxation and increased rectal compliance but did not significantly alter gastric compliance or visceral perception. Psychological test scores were similar in patients and controls. We conclude that in this group of psychologically normal patients with irritable bowel syndrome, who were not chronic health-care seekers, visceral perception was normal. Ondansetron did not alter gut perception in health or in irritable bowel syndrome.
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PMID:Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distension and serotonin type 3 antagonism. 772 Apr 76

We investigated the possible involvement of 5-HT3 receptors in the colonic motor alterations and abdominal pain evoked by rectal distension (RD) in rats, under normal and inflammatory conditions. Responses to RD were evaluated by electromyography in rats treated with 5-HT3 antagonists (ondansetron and cilansetron, 0.1 and 1 mg/kg, intraperitoneally), before and 3 days after intrarectal administration of TNB/ethanol. RD evoked a significant (P < 0.05) and gradual inhibition of the occurrence of colonic spike bursts (SB) and a gradual increase in abdominal SB from 11 mm in diameter on wards. Ondansetron and cilansetron (0.1 mg/kg) significantly reduced both the colonic (62 and 66%, respectively) and the abdominal response (28 and 61%, respectively) for an 11 mm diameter of RD. After TNB/ethanol, both colonic and abdominal responses to RD were significantly (P < 0.05) enhanced and appeared for a lower diameter (9 mm) (colon: 4.8 +/- 0.9 vs 8.4 +/- 1.1, abdomen: 7.7 +/- 1.5 vs 0.5 +/- 0.4). Cilansetron (0.1, 1 mg/kg) significantly (P < 0.05) attenuated the TNB-induced colonic motor inhibition, while ondansetron and cilansetron (0.1, 1 mg/kg) reduced the TNB-induced increase in abdominal response. We conclude that 5-HT and 5-HT3 receptors mediate RD-induced viscerosensitive alterations in rats, both in normal conditions and during TNB-induced rectocolitis. However, the relative efficacy of the 5-HT3 receptor antagonists depends on the experimental conditions (intact or inflamed bowel) and does not appear to increase with the dose.
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PMID:Influence of 5-HT3 receptor antagonists in visceromotor and nociceptive responses to rectal distension before and during experimental colitis in rats. 772 Dec 33

There was a significant increase in potassium-stimulated release of 3H-[5-HT] from hippocampal slices taken from rats withdrawn from chronic ethanol treatment, compared with control-treated rats. The anxiogenic behaviour observed 12 h after ethanol withdrawal was inhibited by the 5-HT1A partial agonist, buspirone (200 micrograms/kg s.c.), indicating that the increased 5-HT release might underlie the anxiogenic response. The ex-ethanol treated rats showed impaired habituation of motor activity in the holeboard and a reduced exploratory response. The latter, but not the former, were reversed by the 5-HT3 receptor antagonist, ondansetron (0.01 microgram/kg i.p.). Ondansetron was without effect on working memory errors, but significantly increased the number of reference memory errors made by the ex-ethanol group. It also had a significantly anxiogenic effect in this group. These results suggest that the chronic ethanol treatment changes the 5-HT system and has long-lasting effects on the function of 5-HT3 receptors.
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PMID:The role of 5-HT in the anxiogenic effects of acute ethanol withdrawal and in the long-lasting cognitive deficits. 774 45

Selective 5-HT3 receptor antagonists such as ondansetron are potent antiemetics for chemotherapy-induced emesis. Ondansetron has been shown to be highly effective in preventing nausea and vomiting in children treated with chemotherapy and/or radiotherapy. However, its high cost may limit its application. A "physician profile" provided by the hospital pharmacy and a questionnaire survey conducted amongst the attending physicians of the hematology/oncology division of a children's hospital showed wide variation in ondansetron use. This variation was evident for both the indications of use and the schedule of administration. Moreover, 80% of the physicians were not aware of the actual cost of ondansetron. In order to reduce this variation, which may affect the quality of care and increase costs unnecessarily, guidelines have been developed for the use of antiemetic drugs in pediatric oncology patients at this institution.
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PMID:Variation in the use of ondansetron as an antiemetic drug in children treated with chemotherapy. 775

The 5-HT3 receptor antagonist ondansetron has previously been reported to improve cognition in the mouse, rat and marmoset in a variety of behavioural paradigms. The present study used the Stone maze to test the effect of ondansetron on the deficit caused by scopolamine in the performance of a highly complex spatial memory task in the rat. Ondansetron administered over a large dose range (1.0 ng kg-1-1.0 micrograms kg-1, i.p., b.d.) for a period of 10-15 days failed to attenuate the scopolamine deficit. Indeed at one dose level ondansetron (100 ng kg-1, i.p., b.d.) administered in combination with scopolamine (0.5 mg kg-1, i.p.) significantly potentiated the deficit, compared with the performance of rats receiving scopolamine alone.
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PMID:Ondansetron fails to attenuate a scopolamine-induced deficit in a Stone maze task. 784 77

Latent inhibition (LI) is a behavioural phenomenon whereby preexposure to a stimulus without reinforcement interferes with the formation of subsequent associations to that stimulus. Using preexposure to a tone stimulus which subsequently serves as a conditioned stimulus for suppression of licking, we have confirmed that LI is disrupted by a low dose of amphetamine. Haloperidol was able to prevent this effect of amphetamine. Ondansetron, a selective and potent 5HT3 receptor antagonist, was also shown to be effective at blocking the amphetamine-induced disruption of LI at a dose of 0.01 mg/kg, but not at 0.1 mg/kg. In addition, it was demonstrated that ondansetron could enhance LI; using only ten preexposures, no LI was obtained in the saline group, but was apparent in animals given ondansetron, an effect which has been previously shown with haloperidol. Haloperidol, at the higher dose used, reduced suppression of licking, however, ondansetron at the effective dose had no such effect. It is concluded that ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed.
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PMID:Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: implications for a possible antipsychotic action of ondansetron. 785 29

5-HT3 receptor antagonists, e.g. MDL72222, ondansetron and ICS205-930, have been previously reported to block a morphine (1.5 mg/kg)-induced conditioned place preference in rats. This finding suggests that these drugs may modify the morphine discriminative stimulus which underlies place conditioning. To study this further we have examined the effects of MDL72222, ondansetron and ICS205-930 against a morphine discriminative stimulus using a two-choice, food reinforced, operant paradigm. In an attempt to provide consistency with previous place conditioning studies, a morphine training dose of 1.5 mg/kg was used in addition to a higher 3 mg/kg dose which was studied in separate animals. Stimulus control of behaviour was attained at both morphine training doses, the characteristics of each being consistent with an effect at the mu opioid receptor. Ondansetron (0.001-1 mg/kg), MDL72222 (0.1-3 mg/kg), and ICS205-930 (0.001-1 mg/kg) all failed to consistently antagonise the morphine cue at both training doses, although a mild attenuation was seen in the 1.5 mg/kg group following pretreatment with an intermediate dose of ondansetron and ICS205-930 (both 0.01 mg/kg). The present results therefore suggest hat 5-HT3 antagonists do not block a morphine discriminative state, at least in rats.
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PMID:Effect of 5-HT3 receptor antagonists on the discriminative stimulus properties of morphine in rats. 787 Sep 98


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