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)

This study was carried out to assess the efficacy of oral ondansetron, a new 5HT3 receptor antagonist, in patients undergoing thyroid surgery. It included 60 patients, randomly assigned to two groups, and receiving orally, 1 h before induction of anaesthesia, either 8 mg of ondansetron (n = 29) or a placebo (n = 30). One patient was excluded. The same anaesthetic protocol, consisting of 3 to 5 micrograms.kg-1 of fentanyl, 4 to 6 mg.kg-1 of thiopentone, and 0.5 mg.kg-1 of atracurium, was used in all. Anaesthesia was maintained with 50% nitrous oxide in oxygen with 0.8 to 1% endtidal concentration of isoflurane and additional boluses of 0.1 mg of fentanyl as required. The incidence and intensity of nausea, graded mild, moderate or severe, and the incidence of vomiting were recorded postoperatively. During the first twelve hours after surgery, 40% of patients in the placebo group had nausea (16.7% mild, 20% moderate and 6.7% severe), and 50% vomited. In the ondansetron group, nausea and vomiting occurred in 13.8% and 20.4% of patients respectively. The 4 patients in the latter group complained of major nausea. The differences between the groups were statistically significant: p = 0.025 for nausea and p = 0.042 for vomiting. It is concluded that oral ondansetron, 8 mg taken orally 1 h before surgery, significantly reduces the incidence of nausea and vomiting during the first twelve postoperative hours. As it is easy to use and has no side-effects, it might be of interest in day-case surgery patients, despite its high cost.
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PMID:[Prevention of postoperative nausea and vomiting by ondansetron]. 147 80

With computer modeling, an initial three-component pharmacophore for specific 5-HT3 receptor ligands ICS-205-930 (1), ondansetron (2), zacopride (3), and 3-[2-(guanidinylmethyl)-4-thiazolyl]indol (4) has been identified. Two parts represent electrostatic interactions, one as a hydrogen-bond-donating interaction and the other as a hydrogen-bond-accepting interaction. The third part is represented by a plane in which the lipophilic aromatic groups align. The generation of the pharmacophore relies on the interactions of these ligands with probe atoms representative of a possible hydrogen-bond donor or hydrogen-bond acceptor within the receptor. A carboxylate oxygen was used as a hydrogen-bond-accepting probe and a serine-like hydroxyl was utilized as a hydrogen-bond-donating probe.
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PMID:An initial three-component pharmacophore for specific serotonin-3 receptor ligands. 214 34

Ondansetron, a selective 5-HT3 receptor antagonist, has recently been shown, in a dose of 8 mg, to be superior to 1.25 mg droperidol in preventing postoperative vomiting. There are indications that a dose of 4 mg of ondansetron may be just as effective in reducing postoperative nausea and vomiting as a dose of 8 mg. The aim of this study was to evaluate the efficacy and the adverse effects of 4 mg ondansetron in the prevention of postoperative nausea and vomiting compared to droperidol in patients undergoing surgery with inhalation anaesthesia supplemented with alfentanil. METHODS. Following institutional approval, 40 ASA physical status I and II women scheduled for minor gynaecological surgery gave informed consent to participate in this randomized, double-blind comparative study. Five minutes before induction of general anaesthesia, 20 patients received a single intravenous (i.v.) dose of 4 mg of ondansetron and the remaining 20 received 1.25 mg droperidol i.v. Anaesthesia was induced with 2.1-4 mg/kg of thiopental and 0.1 mg of alfentanil i.v. and maintained with 65% nitrous oxide and 1.5%-3% enflurane in oxygen. On pain stimuli another 0.2-0.4 mg of alfentanil was given. Total effective antiemetic response was defined as the absence of nausea and vomiting for 24 h postoperatively. The incidence of nausea, vomiting and the number of patients showing total antiemetic response as well as the incidence of adverse effects were compared with the chi 2 test and P < 0.05 was considered significant. RESULTS. Patients were similar with respect to age, height, body weight and total anaesthetic agents received. Duration of anaesthesia and the time until awakening was not significantly different among groups. Postoperatively 7 out of 20 patients given 4 mg of ondansetron and 3 out of 20 patients with droperidol vomited (n.s.). The incidence of nausea was 11 out of 20 in the ondansetron group, and 4 out of 20 in the droperidol group (P < 0.05). Sixteen patients in the droperidol group and 8 patients in the ondansetron group showed a total effective antiemetic response (P < 0.05). Postoperative sedation and well-being scores did not differ significantly among groups. CONCLUSION. Our results show that for the prevention of postoperative nausea and vomiting 4 mg of Ondansetron was inferior to 1.25 mg of droperidol. The drugs were given intravenously prior to general anaesthesia for minor gynaecological surgery with nitrous oxide and enflurane in oxygen supplemented with small boluses of alfentanil.
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PMID:[Ondansetron as prophylaxis for postoperative nausea and vomiting. A prospective randomized double-blind comparative study with droperidol]. 797 72

The R- and S-enantiomers of the 4,5,6,7-tetrahydro-1H-benzimidazole derivatives 3-8 were prepared by optical resolution. Each R-isomer, except for 3, was almost two orders of magnitude more potent than its S-isomer as a 5-hydroxytrptamine (5-HT3) receptor antagonist, as judged from they effect on the von Bezold-Jarisch reflex (B. J. reflex) in rats, the contraction of isolated guinea-pig colon and the receptor-binding affinity. The (--)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] derivative 6R.HCl (ramosetron = YM060) and (--)-(R)-5-[(1-indolinyl)carbonyl] derivative 4R.HCl (YM114 = KAE-393) given p.o. were hundreds of times more potent than 1 (ondansetron) and 2 (granisetron) in their inhibitory effects on cisplatin-induced emesis in ferrets and restraint stress-induced increases in fecal pellet output in rats. Three-dimensional molecular modeling studies suggested that the 'chiral selection' of the enantiomers might be influenced by the steric repulsion between the aromatic ring part and the conformationally restricted 4,5,6,7-tetrahydro-1H-benzimidazole ring in "equatorial-twist" conformation. In our pharmacophore model for the 5-HT3 receptor antagonist, a basic center exists at the left side of the aromatic-carbonyl plane when viewing from the aromatic part with the carbonyl oxygen atom upwards, whereas the "handedness" is ambiguous in the previously proposed model.
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PMID:Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. III. Pharmacological evaluations and molecular modeling studies of optically active 4,5,6,7-tetrahydro-1H-benzimidazole derivatives. 885 65

Efficiency of ondansetron, a selective 5-HT3 receptor antagonist, in prevention of postoperative nausea and vomiting in 40 ASA I-II patients who will undergo emergency intraabdominal operations is studied in a randomized double-blind and placebo controlled study. Patients of no premedication are administered 4 mg i.v. ondansetron or placebo (saline) before induction. Thiopental (4 mg/kg) was used for induction, succinylcholine (2 mg/kg) for muscular relaxation, and 50% nitrous oxide in oxygen and isoflurance (0.8-1.5%) for the maintenance of anesthesia, and fentanyl and norcuron were administered when necessary. Vital signs were closely monitored and recorded during anesthesia and early postoperative period. Study is carried out during postoperative 0-1 h, 1-2 h and 2-24 h periods. Nausea scores and emesis were recorded during 0-1 and 1-2 h periods. Ondansetron was found significantly more effective than placebo (p < 0.05 and p < 0.05). Although is was effective during 2-24 h period, the difference was not statistically significant (p > 0.05). No significant difference was observed between the groups in terms of vital findings, laboratory findings and side effects (p > 0.05). Therefore it is concluded that administration of prophylactic i.v. ondansetron to patients undergoing emergency intraabdominal operations is effective in prevention of nausea and vomiting without any significant side effects.
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PMID:Prophylactic administration of ondansetron in emergency intraabdominal operations. 899 79

1. It has been widely accepted that the rat aortic depressor nerve contains only baroreceptors. However, the experiments which have provided these negative data have employed whole aortic nerve recording. In the present study, the technical difficulties associated with recording single fibres in vivo, from the rat aortic nerve (diameter 25-50 microm), have been surmounted using a small tip, glass suction electrode technique. 2. Upon switching from normocapnic hyperoxia to hypercapnic hypoxia, irregularly firing units (n = 13) appeared and these were significantly excited by intravenous injections of sodium cyanide (20 microg) but not by rises in arterial blood pressure induced by methoxamine (an alpha1-adrenoreceptor agonist; 10 microg). Inhalation of 100 % oxygen rapidly and reversibly silenced, or profoundly reduced, ongoing activity. 3. Intravenous injection of phenylbiguanide (PBG; a 5-HT3 receptor agonist; 8 microg) strongly stimulated the chemoreceptors and was followed by a period of chemodepression (3-21 s). In contrast none of the single fibre baroreceptors recorded (n = 15) were excited by PBG but all significantly increased their discharge in response to the increases in arterial blood pressure associated with methoxamine and cyanide. Both the excitatory and inhibitory effects of PBG on the chemoreceptor fibres were abolished by ondansetron (a 5-HT3 receptor antagonist: 1 mg kg-1 i.v.; n = 5 animals) whilst the chemoexcitatory action of cyanide was preserved. 4. It is concluded that there are chemoreceptor afferents contained in the aortic nerve of the Sprague-Dawley rat. The 5-HT3 receptor appears not to be a pre-requisite for aortic body chemoexcitation.
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PMID:Activity of aortic chemoreceptors in the anaesthetized rat. 988 53

The present study uses increased atmospheric pressure as an ethanol antagonist to test the hypothesis that allosteric coupling pathways in the GABA(A) receptor complex represent initial sites of action for ethanol. This was accomplished using behavioral and in vitro measures to determine the effects of pressure on ethanol and other GABAergic drugs in C57BL/6 and LS mice. Behaviorally, exposure to 12 times normal atmospheric pressure (ATA) of a helium-oxygen gas mixture (heliox) antagonized loss of righting reflex (LORR) induced by the allosteric modulators ethanol and pentobarbital, but did not antagonize LORR induced by the direct GABA agonist 4,5,6,7-tetrahydroisoxazolo-pyridin-3-ol (THIP). Similarly, exposure to 12 ATA heliox antagonized the anticonvulsant effects verses isoniazid of ethanol, diazepam and pentobarbital. Biochemically, exposure to 12 ATA heliox antagonized potentiation of GABA-activated 36Cl-uptake by ethanol, flunitrazepam and pentobarbital in LS mouse brain preparations, but did not alter GABA-activated 36Cl- uptake per se. In contrast to its antagonist effect versus other allosteric modulators, pressure did not antagonize these behavioral or in vitro effects induced by the neuroactive steroid, 3alpha-hydroxy-5beta-pregnan-20-one (3alpha,5beta-P). These findings add to evidence that pressure directly and selectively antagonizes drug effects mediated through allosteric coupling pathways. The results fit predictions, and thus support the hypothesis that allosteric coupling pathways in GABA(A) receptors represent initial sites of action for ethanol. Collectively, the results suggest that there may be common physicochemical and underlying structural characteristics that define ethanol sensitive regions of receptor proteins and/or their associated membranes that can be identified by pressure within (e.g., GABA(A)) and possibly across (e.g., GABA(A), NMDA, 5HT3) receptors.
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PMID:In vivo and in vitro hyperbaric studies in mice suggest novel sites of action for ethanol. 1009 Jun 41

Cardiac sympathetic afferents are known to reflexly activate the cardiovascular system, leading to increases in blood pressure, heart rate, and myocardial contractile function. During myocardial ischemia, these sensory nerves also transmit the sensation of pain (angina pectoris) and cause tachyarrhythmias. The authors' laboratory has been interested in defining the mechanisms of activation of this neural system during ischemia and reperfusion. During these periods, reactive oxygen species, particularly hydroxyl radicals, are produced from the breakdown of purine metabolites and lead to stimulation of sympathetic (and vagal) ventricular chemosensitive nerve endings. For example, stimulation with hydrogen peroxide leads to a small reflex increase in blood pressure from the predominant sympathetic afferent activation that is reduced by simultaneous activation of cardiac vagal afferents (known to exert predominantly depressor reflexes). Central integration of these two opposing reflexes likely occurs at several regions of the brain stem, including the nucleus tractus solitarii, where neural occlusion occurs during simultaneous cardiac sympathetic and vagal-afferent stimulation. Activation of platelets also appears to play a role during myocardial ischemia, leading to local release of serotonin (5HT), which, through a 5HT3 mechanism, stimulates sympathetic afferents. Finally, regional changes in pH from lactic acid (but not hypercapnia), stimulate ventricular afferents and may activate kallikrein to increase bradykinin (BK), which, in turn, breaks down arachidonic acid to form prostaglandins. Prostaglandins sensitize cardiac sympathetic afferents to BK. Thus, stimulation of cardiac sympathetic afferents during ischemia and reperfusion and the resulting reflex events form a multifactorial process resulting from activation of a number of chemical pathways in the myocardium.
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PMID:Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion. Mechanisms and reflexes. 1145 9

Activation of cardiac sympathetic afferents during myocardial ischaemia causes angina and induces important cardiovascular reflex responses. Reactive oxygen species (ROS) are important chemical stimuli of cardiac afferents during and after ischaemia. Iron-catalysed Fenton chemistry constitutes one mechanism of production of hydroxyl radicals. Another potential source of these species is xanthine oxidase-catalysed oxidation of purines. Polymorphonuclear leukocytes (PMNs) also contribute to the production of ROS in some conditions. The present study tested the hypothesis that both xanthine oxidase-catalysed oxidation of purines and neutrophils provide a source of ROS sufficient to activate cardiac afferents during ischaemia. We recorded single-unit activity of cardiac afferents innervating the ventricles recorded from the left thoracic sympathetic chain (T1-5) of anaesthetized cats to identify the afferents' responses to ischaemia. The role of xanthine oxidase in activation of these afferents was determined by infusion of oxypurinol (10 mg kg(-1), I.V.), an inhibitor of xanthine oxidase. The importance of neutrophils as a potential source of ROS in the activation of cardiac afferents during ischaemia was assessed by the infusion of a polyclonal antibody (3 mg ml(-1) kg(-1), I.V.) raised in rabbits immunized with cat PMNs. This antibody decreased the number of circulating PMNs and, to a smaller extent, platelets. Since previous data suggest that platelets release serotonin (5-HT), which activates cardiac afferents through a serotonin receptor (subtype 3,5-HT3 receptor) mechanism, before treatment with the antibody in another group, we blocked 5-HT3 receptors on sensory nerve endings with tropisetron (300 microg kg(-1), I.V.). We observed that oxypurinol significantly decreased the activity of cardiac afferents during myocardial ischaemia from 1.5 +/- 0.4 to 0.8 +/- 0.4 impulses s(-1). Similarly, the polyclonal antibody significantly reduced the discharge frequency of ischaemically sensitive cardiac afferents from 2.5 +/- 0.7 to 1.1 +/- 0.4 impulses s(-1). However, pre-blockade of 5-HT3 receptors eliminated the influence of the antibody on discharge activity of the afferents during ischaemia. This study demonstrates that ROS generated from the oxidation of purines contribute to the stimulation of ischaemically sensitive cardiac sympathetic afferents, whereas PMNs do not play a major role in this process.
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PMID:Xanthine oxidase, but not neutrophils, contributes to activation of cardiac sympathetic afferents during myocardial ischaemia in cats. 1218 3

5-HT(3) receptor antagonists are clinically available for treating patients with irritable bowel syndrome (IBS) but their use is restricted because of a link with some episodes of ischaemic colitis. However, the role of 5-HT3 receptors in regulating colonic blood flow has not been systematically investigated. Thus, we examined acute and chronic treatment with alosetron, a potent and selective antagonist of the 5-HT3 receptor, on baseline colonic blood flow and haemodynamic responses during occlusion and reactive hyperaemia in the pentobarbitone-anaesthetized rat. Colonic haemodynamics were assessed using ultrasonic recordings of superior mesenteric blood flow (MBF) and laser Doppler recordings of colonic vascular perfusion (VP). Blood pressure (BP) was also monitored and in some experiments tissue oxygen was detected polarographically. Alosetron (10, 30, 100 microg kg(-1), i.v.) had no effect on baseline haemodynamics nor responses to nitric oxide synthase inhibition with N(omega)-nitro-l-arginine methyl ester (l-NAME) (16 mg kg(-1)). Arterial occlusion (5 min) reduced MBF (-98.6 +/- 0.6%) and VP (-70.7 +/- 5.4%) followed by a post-occlusion reactive hyperaemia (MBF = +94.5 +/- 19.1%; VP = +60.0 +/- 22.3%) the magnitude of which was unchanged following acute (30 microg kg(-1)) or chronic alosetron administration (0.5 mg kg(-1) twice daily, 5 days). Alosetron did not significantly alter baseline colonic blood flow in the anaesthetized rat; nor did it interfere with vascular control mechanisms activated during occlusion and reactive hyperaemia.
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PMID:Impact of 5-HT3 receptor blockade on colonic haemodynamic responses to ischaemia and reperfusion in the rat. 1759 42


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