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)

There is interest in the development of antiemetics other than dopamine receptor antagonists for the treatment of postoperative nausea and vomiting. A ferret model of morphine-induced emesis may have wider application in evaluating newer agents than the apomorphine dog model. This study describes the conditions for morphine-induced emesis in ferrets and evaluates five antiemetics that are prototypical of three different mechanisms. The average numbers of vomiting and retching episodes induced by morphine (0.1-2.5 mg/kg s.c.) were distributed as a bell-shaped curve. Maximum number of vomits occurred at 0.3 mg/kg (11.8 +/- 2.1 vomits; 45 +/- 12.5 retches). Antiemetics or vehicle were given i.v. 5 min prior to morphine while each ferret was maintained under isoflurane-O2 anesthesia. Ondansetron, a 5-HT3 receptor antagonist, reduced vomiting episodes by 47% and 70% (3 and 10 mg/kg). Granisetron, a 5-HT3 receptor antagonist was inactive at doses of 0.1, 1.0, 3.0 and 10 mg/kg. Metoclopramide reduced vomiting episodes by 48% and 82% (3 and 10 mg/kg). Droperidol reduced vomiting episodes by 84% at 3 mg/kg. Naloxone reduced vomiting episodes by 91% and 43% at doses of 0.1 and 1.0 mg/kg. In most cases, prolonged latency times to the first episodes accompanied the reduction in total numbers of episodes. The significant reduction of morphine-induced emesis in the ferret by ondansetron, metoclopramide and droperidol is consistent with the reduction of postoperative emesis in man by these compounds when morphine was a component of the anesthetic regimen. These results suggested that the morphine ferret model may be useful for evaluating compounds having the potential for preventing and treating postoperative vomiting.
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PMID:The effects of different antiemetic agents on morphine-induced emesis in ferrets. 822 24

5-Hydroxytryptamine (5-HT) is a mitogen for selected cell types. We have reported that 5-HT is an autocrine growth factor for functioning human pancreatic carcinoid (BON) cells; autocrine growth effect is transmitted by 5-HT1A but not 5-HT1C/2 receptors, activation of which decreases cyclic AMP production through a pertussis toxin-sensitive inhibitory GTP-binding protein. In this study, the effect of 5-HT3 receptor antagonist, ondansetron, on BON was examined. Ondansetron did not affect growth of BON cells and also affected neither stimulation of phosphatidylinositol hydrolysis or inhibition of cyclic AMP production evoked by 5-HT in BON cells. Ondansetron, however, inhibited mobilization of intracellular calcium evoked by 5-HT. Present findings suggest that BON cells possess 5-HT3 receptors, but their roles in pancreatic carcinoid cells are still unknown.
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PMID:Effect of 5-HT3 receptor antagonist (ondansetron) on functioning human pancreatic carcinoid cells. 825 12

The potential roles of central and peripheral 5-HT3 receptors in the secretion of prolactin, adrenocorticotropic hormone (ACTH), corticosterone and renin was investigated. Male rats received the 5-HT3 antagonist ondansetron (0, 0.1 or 1 mg/kg i.p.), 30 min prior to injections of the serotonin (5-HT) releaser, p-chloroamphetamine (PCA; 0, 3 or 8 mg/kg i.p.). Blood samples were collected 60 min after PCA for radioimmunoassays of plasma prolactin, ACTH, corticosterone and renin concentrations. PCA significantly elevated secretion of each of these hormones. Pretreatment with the 5-HT3 antagonist, ondansetron, significantly attenuated the PCA-induced elevation of prolactin secretion, suggesting that 5-HT3 receptors contribute to the serotonergic stimulation of prolactin secretion. Ondansetron did not modify effects of PCA on ACTH, corticosterone or renin secretion. To determine whether the 5-HT3 receptor role in prolactin secretion is mediated in the brain, the endocrine effects of intracerebroventricular (i.c.v.) injections of 5-HT (30 micrograms/kg) or the 5-HT3 agonist, 2-methylserotonin (1, 20 or 200 micrograms/kg) were evaluated. Both 5-HT and 2-methylserotonin significantly elevated plasma prolactin levels 15 min postinjection. However, ondansetron (1 mg/kg i.p.) did not antagonize these actions. Both 5-HT and 2-methylserotonin also increased plasma ACTH and corticosterone concentrations. Finally, 5-HT suppressed, while 2-methylserotonin stimulated renin secretion. None of the hormonal effects of i.c.v. injected 5-HT or 2-methylserotonin were altered by ondansetron. Thus, the results suggest that peripheral, but not central 5-HT3 receptors are involved in the stimulation of prolactin secretion. Furthermore, 5-HT3 receptors do not mediate the serotonergic stimulation of ACTH, corticosterone, or renin secretion.
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PMID:Investigation of the role of 5-HT3 receptors in the secretion of prolactin, ACTH and renin. 826 57

Serotonin is one of the many neurotransmitters involved in nociception. Serotonin antagonists may therefore reduce postoperative pain. In the present study we examined whether the new 5-HT3 receptor antagonist GR 38032F (ondansetron) reduced postoperative pain after minor surgery and compared its effectiveness with that of lysin acetyl salicylate (Aspisol). METHODS. A series of 100 patients of both sexes who were undergoing minor surgery were enrolled in this study. Patients who did not need analgesic medication within the first 3 h after surgery were regarded as "dropouts", and the rest were studied for 24 h. In a preliminary study (n = 19) patients received ondansetron i.v. in increasing dosages (6, 12, 24, 48, 96 and 128 micrograms.kg-1) to evaluate the analgesic potency of this drug. In the main double-blind, randomized, study (n = 81), three groups were formed, and patients received 50 micrograms.kg-1 or 100 micrograms.kg-1 ondansetron i.v. or saline only i.v. Analgesia was evaluated by visual analogue (VAS) and verbal rating scales (VRS). If pain persisted patients received 1.8 g lysin acetylsalicylate (LAS) i.v. RESULTS. There were 6 (out of 19) patients in the preliminary study and 36 (out of 81) patients in the main study who were dropouts; that is to say they did not require any analgesic medication within the first 3 h, but 12 of these dropouts needed analgesic medication more than 3 h after end of surgery. Pain was reduced by 82% from baseline in 7 out of 13 patients in the preliminary study (11 men, 2 women). In the main study (n = 45, 28 men, 17 women) 100 micrograms.kg-1 ondansetron did not show a better analgesic effect than 50 micrograms.kg-1, and there was no significant difference between ondansetron and saline. VAS showed a reduction in pain from 6.9 +/- 2.0, 6.8 +/- 1.5 and 6.6 +/- 1.8 to 4.1 +/- 2.4, 3.4 +/- 2.2 and 3.4 +/- 2.1 in the 50 micrograms.kg-1, 100 micrograms.kg-1 and saline groups, respectively, within 60 min after i.v. application. VRS diminished from 2.5 +/- 0.5, 2.5 +/- 0.6 and 2.4 +/- 0.5 to 1.7 +/- 0.7, 1.5 +/- 0.8 and 1.5 +/- 0.7, respectively. There were 26 patients who experienced no pain relief in response to ondansetron or placebo and who therefore received LAS, and 21 of these then experienced significant pain reduction. CONCLUSION. Pain after minor surgery does not appear to be a major problem. For 42 out of 100 patients no analgesics were needed within the first 3 h after end of surgery. Ondansetron was no more effective than placebo in reducing postoperative pain. Lysin acetylsalicylate, however, may be an effective alternative to opioids for the treatment of postoperative pain.
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PMID:[Postoperative pain therapy. The efficacy of a serotonin antagonist (GR 38032F;ondansetron) and the prostaglandin synthesis inhibitor lysin acetylsalicylate (Aspisol)]. 827 93

In some patients with the irritable bowel syndrome, rectal urgency and discomfort are major clinical problems and, under experimental conditions, these symptoms are perceived at lesser volumes of rectal distension than they are in asymptomatic controls. Further, a 5-hydroxytryptamine type-3 receptor antagonist increased the threshold for rectal discomfort in irritable bowel syndrome. Our aims were, (a) to measure rectal sensation during isobaric distensions of the rectum, and (b) to test the effect of another selective 5HT3-antagonist, ondansetron 0.15 mg/kg, on rectal sensitivity, colonic tone, rectal tone and manometric responses. Ten healthy volunteers and five patients with diarrhoea-predominant irritable bowel syndrome were studied. A multilumen barostat-manometric assembly was placed in the descending colon, and a second barostat balloon was positioned in the rectum. Tone in the wall of the colon and rectum was measured by the barostat balloon volume during a constant pressure clamp, while intraluminal pressures were recorded by manometry; perceived sensations were also recorded before and after the intravenous administration of ondansetron or placebo in blinded fashion. Rectal resistance to stretch was greater and rectal urgency was induced by lower distending pressures in irritable bowel syndrome, however, basal tone in the rectum was similar in health and irritable bowel syndrome. Ondansetron did not change rectal sensitivity (first sensation or urgency) or tone. Rectal distension did not alter tone in the descending colon or colonic manometry; ondansetron did not influence any index of colonic function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a 5HT3-antagonist (ondansetron) on rectal sensitivity and compliance in health and the irritable bowel syndrome. 828 Aug 23

Previous behavioural studies have shown that 5-hydroxytryptamine3 (5-HT3) receptor antagonists either block or have no effect on amphetamine-induced effects. The present experiments investigated whether or not the highly selective 5-HT3 receptor antagonist ondansetron would affect the anorectic effect of a small dose (1 mg/kg) of d-amphetamine. Nondeprived male rats were tested in two feeding paradigms: consumption of a palatable sweetened mash and ingestion of a 3% sucrose solution. Ondansetron (10-100 micrograms/kg) did not antagonize amphetamine-induced anorexia; instead, in both paradigms consumption was reduced still further when the 5-HT3 antagonist was given in conjunction with amphetamine. Ondansetron given alone had significant effects on consumption, but the direction of the effect differed according to the paradigm. Sweetened mash intake was significantly increased at 30 and 100 micrograms/kg, while sucrose ingestion was significantly reduced at 10 and 30 micrograms/kg ondansetron. It is suggested that ondansetron has two opposing effects on intake, one of which (hyperphagia) can be masked by d-amphetamine, leaving an anorectic effect that augments that of d-amphetamine.
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PMID:The selective 5-HT3 receptor antagonist, ondansetron, augments the anorectic effect of d-amphetamine in nondeprived rats. 833 20

Serotonin is a neurotransmitter involved in chemotherapy-induced emesis and ondansetron is a new drug endowed with selective antagonism against the 5HT3 receptors. Phase I-II studies have demonstrated its activity against acute emesis after single-dose cisplatin, reporting particularly low toxicity; in comparative studies with high-dose metoclopramide, it has been proved to be more effective and completely devoid of extrapyramidal side effects. Ondansetron has shown its activity and safety also in multiple-day cisplatin regimens. Its antiemetic efficacy is improved by the addition of dexamethasone. Preliminary data suggest its role also when used in single-dose administration. Its activity in the delayed phase of cisplatin emesis needs to be further explored.
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PMID:Cisplatinum based chemotherapy: role of the antiserotoninergic ondansetron in prevention of emesis. 837 Nov 30

5-HT3 receptors are abundant in central dopamine (DA) terminal areas. They do not affect basal DA turnover but appear to modulate DA release by e.g. morphine and nicotine. The interpretation of these findings is uncertain, and it is unclear whether 5-HT3 receptors also influence the activity of compounds such as amphetamine and cocaine, which act more directly on the DA synapse. Variable-interval (VI), threshold-current hypothalamic self-stimulation can provide a continuous index of central dopaminergic activity, but is relatively insensitive to changes in 5-HT and thus offers a means of investigating this question. In the present study, a selective 5-HT3 receptor antagonist, ondansetron (GR 38032F) (1.0 to 1000 micrograms/kg sc), had no effect on VI self-stimulation, nor did a 100 micrograms/kg dose affect facilitation of responding by d-amphetamine (500 micrograms/kg ip). Ondansetron (100 micrograms/kg) reduced the initial depression of self-stimulation by high-dose nicotine (400 micrograms/kg), but not the ensuing facilitation. Similar results were obtained in rats "sensitized" to nicotine by prior chronic exposure. These results support the proposal that 5-HT3 receptors, normally quiescent under basal conditions, mediate the excitatory effect of compounds acting upstream from the DA neuron, such as nicotine, but do not affect the dopaminergic synapse directly.
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PMID:The effect of a 5-HT3 receptor antagonist, ondansetron, on brain stimulation reward, and its interaction with direct and indirect stimulants of central dopaminergic transmission. 838 82

Despite recent advances in control of acute emesis, delayed nausea and vomiting following cisplatin-based chemotherapy remain a significant cause of treatment-related morbidity. Ondansetron, a selective 5HT3 receptor antagonist, is effective in preventing acute emesis in the initial 24-h period following high-dose cisplatin. The efficacy and safety of ondansetron in preventing the delayed emesis syndrome during days 2-5 after cisplatin (> or = 100 mg/m2) were evaluated in a double-blind, placebo-controlled multicentre trial. 50 patients having two or fewer emetic episodes during the first 24 h were randomised to receive ondansetron (16 mg) or placebo orally three times daily beginning 24 h after cisplatin. Rates of complete control of emesis were higher in ondansetron-treated patients during each study day, 59-78%, compared with 39-50% in placebo-treated patients, but the differences were statistically superior only on the third study day (P = 0.009). 40% of patients in the ondansetron treatment arm and 33% treated with placebo had complete control of emesis during the entire 4-day study period (P = 0.648). Withdrawal from study due to nausea and vomiting occurred in 13% of ondansetron-treated patients compared with 33% in the placebo arm (P = 0.102). Control of nausea was better with ondansetron, but differences were not statistically significant. Adverse effects of oral ondansetron given in this dose schedule were minimal. These data suggest that the delayed emesis syndrome may be partially mediated through the 5HT3 receptor, but that a serotonin antagonist alone provides inadequate control. Further investigation of ondansetron-based therapy in this clinical setting is warranted.
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PMID:Delayed emesis following high-dose cisplatin: a double-blind randomised comparative trial of ondansetron (GR 38032F) versus placebo. 842 24

Effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on the release of cholecystokinin-like immunoreactivity (CCK-LI) in rat frontal cortex were investigated in conscious, unrestrained rats using intracerebral microdialysis. The release of CCK-LI was augmented by perfusion with 100 micrograms/ml veratrine and was fully Ca(2+)-dependent and tetrodotoxin-sensitive. Ondansetron and tropisetron, each at 0.1-1 mumol/l, decreased concentration-dependently the veratrine-evoked efflux of CCK-LI. The reduction of CCK-LI output was approximately 30% when the antagonists were infused at 0.1 mumol/l. The data suggest that 5-HT3 receptor antagonists prevent the release of CCK evoked by endogenous 5-hydroxytryptamine. These drugs may thus represent a novel therapeutic approach in disease states, like anxiety, in which an inappropriately high release of brain CCK or 5-hydroxytryptamine seems to be involved.
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PMID:Inhibition by 5-HT3 receptor antagonists of release of cholecystokinin-like immunoreactivity from the frontal cortex of freely moving rats. 844 79


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