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)

Supraspinal opioid analgesia is mediated in part by connections between the midbrain periaqueductal gray (PAG) and rostral ventral medulla (RVM) which includes the nuclei raphe magnus and reticularis gigantocellularis. Serotonergic 5HT2 and 5HT3 receptor subtypes appear to participate in this pathway since general and selective serotonergic antagonists microinjected into the RVM significantly reduced morphine analgesia elicited from the PAG. Since both an enkephalinergic pathway between the PAG and RVM and intrinsic enkephalinergic cells in the RVM exist, the present study evaluated the abilities of general (naltrexone), mu-selective (beta-funaltrexamine: B-FNA) and delta 2-selective (naltrindole) opioid receptor subtype antagonists microinjected into the RVM to alter morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. Mesencephalic morphine analgesia was significantly reduced after pretreatment in the RVM with naltrexone (1-10 micrograms), B-FNA (0.5-5 micrograms) or naltrindole (0.5-5 micrograms). Naltrexone in the RVM failed to alter basal nociceptive thresholds and none of the opioid antagonists were effective in reducing mesencephalic morphine analgesia when they were microinjected into placements lateral or dorsal to the RVM. These data indicate that mu and delta 2 opioid receptors in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG.
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PMID:Medullary mu and delta opioid receptors modulate mesencephalic morphine analgesia in rats. 825 87

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

The serotonergic system is involved in pain transmission and the 5-hydroxytryptamine (5-HT3) receptor subtype mediates some of these effects at the spinal level. Therefore, we explored the effects of the serotonergic system on nifedipine-induced analgesia by using the 5-HT3 receptor antagonist ondansetron. Male Sprague-Dawley rats were pretreated with ondansetron (1 mg/ kg intraperitoneally) or normal saline. After 15 min, rats received injections of nifedipine (15 mg/kg intraperitoneally) or dimethylsulfoxide (DMSO), solvent for nifedipine, as a control. Nociception was assessed by tail-flick method. Rats treated with nifedipine alone had an increase in tail-flick latency of 122%, as measured by the area under the curve, compared to rats treated with DMSO alone. Pretreatment with ondansetron, however completely blocked the analgesic effect of nifedipine, with tail-flick latency remaining at baseline throughout the measurement period. These results indicate that the 5-HT3 receptor plays an important role in the analgesic response to nifedipine and that medications that block this receptor may decrease the analgesic effectiveness of this type of therapy.
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PMID:Ondansetron blocks nifedipine-induced analgesia in rats. 862 50

The serotonin 5-HT3 receptor is unique among the seven serotonin receptor "families" that have been recognized so far. It functions not as a G-protein coupled but as a direct ion channel gated receptor. Because of the varied neural functions linked to this receptor, intensive research interest has developed in recent years about its basic and clinical pharmacology, which are summarized in this review. Some new agonists and many new antagonists have been developed. These agents have a useful role as selective pharmacologic research probes, and some of them can be used therapeutically as potent and selective anti-nausea and antiemetic drugs, particularly in patients undergoing cancer chemotherapy treatment or general anesthesia procedures. Potential applications of these agents include the treatment of some behavioral disorders in mental disease, drug addiction, and certain types of pain syndromes.
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PMID:5-HT3 receptors: pharmacologic and therapeutic aspects. 878 44

Painful bone metastases are a clear indication for the use of radiotherapy, with reported response rates of up to 85% of patients treated. In an attempt to define the optimal use of palliative radiotherapy when used in this situation, the data for the efficacy, toxicity and choice of dose and fractionation are reviewed. Although there have been some recent trials demonstrating the value of hypofractionated radiation therapy, half-body irradiation and 89-strontium, in general there is a lack of information in this clinical area, particularly on the duration of beneficial effect and on treatment toxicity. The available data suggest that single-fraction radiation is as effective as short-course fractionated treatment, and may be isotoxic when 5HT3 antagonists are used. Future implications for research are discussed.
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PMID:The role of palliative radiotherapy for bone metastases. 885 36

The effects of drugs selectively effecting central serotonergic systems on immobilization-induced analgesia (SIA) were tested in the rat. The drugs were used in dose ranges previously shown to effect emotional processes. SIA was tested using the tail withdrawal method. It was found that pretreatment of rats with para-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis, significantly attenuated SIA, measured immediately after stress session. Ritanserin, a 5-HT2A/2C receptor antagonist, ondansetron, a 5-HT3 receptor antagonist and citalopram, a selective serotonin re-uptake blocker increased the baseline pain threshold, whereas 8-OH-DPAT, a full 5-HT1A receptor agonist and buspirone, a partial 5-HT1A receptor agonist expressing also high affinity towards dopaminergic D2 receptors, were without effect on pain perception and stress induced analgesia. It has been concluded, that modification of SIA by serotonergic drugs probably merely reflects changes in the activity of the 5-HT system on the spinal cord level, with minor, if any, contribution of supraspinal emotional centers.
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PMID:Influence of serotonergic drugs on restraint stress induced analgesia. 886 28

The antiemetic activity of droperidol is attributed to antagonizing the dopaminergic neurons of the chemoreceptor trigger zone. Ondansetron is a serotonin (5HT) receptor antagonist at both peripheral and central 5-HT3 receptor sites with no known action on dopamine-mediated activity. We hypothesized that the combination of these two antiemetics would be more effective than droperidol alone. Women with ASA classified physical status I or II, scheduled for laparoscopic tubal banding, participated in a randomized double-blind clinical trial using a standardized anesthesia regimen. Within 15 min after induction of anesthesia, Group 1 (n = 60) received IV droperidol 1.25 mg and ondansetron 4 mg and Group 2 (n = 60) received IV droperidol 1.25 mg and saline. Before surgery and during recovery at 1, 2, and 24 h, emetic episodes, nausea, pain, drowsiness, medications taken, and adverse events were recorded. The complete response (no emesis, no rescue) for Group 1 was 55 of 60 (91.6%) versus 47 of 60 (78.3%) in Group 2 (P = 0.04). No patient needed rescue antiemetic medication in Group 1, whereas 5 of 60 (8.3%) patients were rescued in Group 2 (P = 0.03). There were seven emetic episodes in five patients in Group 1 and 30 emetic episodes in 12 patients in Group 2 over the 24-h study period (P = 0.03). The time to the first emetic episode was more than twice as long for Group 1 than Group 2 (P = 0.03) and total nausea scores were lower in Group 1 than Group 2 (P = 0.01). The droperidol/ondansetron combination was significantly superior to droperidol in complete response, time to and number of emetic episodes, and the incidence and severity of nausea in women having tubal banding.
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PMID:Droperidol/ondansetron combination controls nausea and vomiting after tubal banding. 917 30

The possibility that 5-hydroxytryptamine (5-HT) acts as a key sensitising agent in the aetiology of irritable bowel syndrome (IBS) is reviewed. The strategic locations of 5-HT and its receptors are described, the most dominant being the 5-HT3 and 5-HT4 type. 5-HT, acting mostly at 5-HT3 or 5-HT3-like receptors, enhances the sensitivity of visceral neurones projecting between the gut and the central nervous systems. 5-HT, acting at 5-HT4 receptors promotes the sensitivity of enteric neurones that react to luminal stimuli. 5-HT4 and 5-HT3 receptors also mediate, respectively, sensitising and physiological actions of 5-HT on gastro-intestinal motor and secretory functions. This distribution implies that some 5-HT3 receptor antagonists might reduce certain symptoms of IBS, such as pain, by reducing the reactivity of the visceral afferent neurones linking the gut with the brain and spinal cord. However, such antagonists are not likely to find widespread clinical acceptance because they can also affect normal lower bowel function and promote constipation. 5-HT4 receptor antagonists, by contrast, reduce 5-HT-induced enteric nerve hypersensitivity without notably affecting the function of the normal bowel. Accordingly, these agents may reduce the symptoms of IBS directly, by reducing the incidence of defecation and diarrhoea and indirectly, by reducing both 'rebound' constipation and the post-prandial discomfort and pain associated with gastrointestinal hyper-reactivity.
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PMID:5-Hydroxytryptamine and functional bowel disorders. 895 36

The discovery of multiple subtypes of the serotonin 5-HT receptor has generated enormous interest over the past few years. Possibly the most exciting, in terms of psychiatric clinical practice, appeared to be the 5-HT3 receptor. Early animal studies suggested that the 5-HT3 receptor antagonists, in addition to their well recognised antiemetic use, might be clinically useful in a number of areas. These included anxiety disorders, psychotic disorders, drug and alcohol abuse disorders, depressive disorders, cognitive disorders, the treatment of pain and the treatment of irritable bowel syndrome. With the exception of antiemetic actions, this review examines these potential therapeutic areas carefully, paying particular attention not only to the animal literature, but to the clinical studies which have resulted from these initial findings. Unfortunately, studies in many of these therapeutic areas have not lived up to their initial promise. Indeed, no clinical studies have yet clearly demonstrated the usefulness of 5-HT3 receptor antagonists in the treatment of CNS disorders. Nonetheless, in view of the absence of published results from double-blind, placebo-controlled studies in many of these therapeutic areas, further research would be useful in confirming the effectiveness, or otherwise, of this group of compounds.
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PMID:The non-antiemetic uses of serotonin 5-HT3 receptor antagonists. Clinical pharmacology and therapeutic applications. 901 Jun 47

The present study examined developmental patterns of antinociception mediated by the spinal 5-HT3 receptor system in the neonatal rat. Intrathecally administered 2-methylserotonin (25-100 micrograms) first produced antinociception against formalin-induced acute inflammatory pain at 10 days postnatally, with effect only at the peak dose (100 micrograms). Intrathecal 2-methylserotonin produced dose-dependent antinociception at 14 and 28 days of age that was attenuated by i.t. pretreatment with the 5-HT3 receptor antagonist MDL-72222 (10 micrograms).
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PMID:Antinociceptive effects of intrathecally administered 2-methylserotonin in developing rats. 902 13


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