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 present study examined the analgesic effects of the serotonin 5-HT3 receptor antagonists ICS-205-930, MDL-7222 and GR-38032F in mice using acute thermal, mechanical and chemical pain tests. Subcutaneous administration (1-10 mg/kg) of these agents did not produce analgesia in either the thermal or mechanical pain tests. However, ICS-205-930, MDL-72222 and GR-38032F all produced dose-dependent analgesia in the chemical pain test, that was not altered by systemic naloxone administration (1 mg/kg, s.c.). Intracerebroventricular administration of these drugs (0.1-10 micrograms) was ineffective in producing analgesia in acute thermal, mechanical and chemical pain tests. These results suggest that peripheral 5-HT3 receptors play a role in chemical, but not thermal or mechanical nociceptive mechanisms.
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PMID:Differential analgesic actions of serotonin 5-HT3 receptor antagonists in the mouse. 252 2

Intraplantar administration of serotonin 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 (1-100 micrograms; 50 microliters) produced dose-related analgesia against formalin-induced acute- and Freunds adjuvant-induced chronic-inflammatory pain in rats. 5-HT3 receptor antagonists had greater effect in the chronic pain test than in the acute paradigm. In both tests, ICS 205-930 was more potent than MDL 72222. These data further support the involvement of peripheral 5-HT3 sites in inflammatory pain, and suggest the utility of selective 5-HT3 receptor antagonists as peripheral analgesics.
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PMID:Peripherally administered serotonin 5-HT3 receptor antagonists reduce inflammatory pain in rats. 261 65

1. Effects of three different categories of antidepressants, imipramine (tricyclic), fluoxetine (selective 5-hydroxytryptamine (5-HT) uptake inhibitor), phenelzine and iproniazid (monoamine oxidase (MAO) inhibitor) on the inward current mediated by 5-HT3 receptors were investigated in rat nodose ganglion neurones. The whole-cell patch-clamp technique was used for recording the 5-HT current. 2. All the antidepressants tested inhibited the peak 5-HT current. The inhibition gradually reached a steady level and the recovery was incomplete when antidepressants were removed. IC50 values for imipramine, fluoxetine and phenelzine were 0.54 microM, 1.3 microM and 4.2 microM respectively. The correspondent Hill coefficients were 0.9, 0.87 and 0.92. 3. The antidepressants examined increased the rate of 5-HT current desensitization. IC50 values for imipramine, fluoxetine and phenelzine on the decrease in desensitization time constant were 0.11 microM, 0.18 microM and 2.4 microM respectively. The correspondent Hill coefficients were 0.9, 1.14 and 1.06. 4. Intracellular applications of the protein kinase inhibitor, H-7 (100 microM), GDP-beta-S (2 mM) and the calcium chelator BAPTA (20 mM) did not affect the 5-HT current and the actions of antidepressants on 5-HT current. 5. These results suggest that the 5-HT3 receptor is an acting site for the therapeutic use of antidepressants. The present observation is also helpful in explaining the analgesic effect of antidepressants seen in pain clinics.
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PMID:Effects of antidepressants on the inward current mediated by 5-HT3 receptors in rat nodose ganglion neurones. 752 57

5-Hydroxytryptamine (5-HT) receptor agonists and antagonists were dosed intravenously (i.v.) and studied for their effects on the depressor cardiovascular pseudoaffective reflex evoked by acute noxious colo-rectal distension in the anaesthetized rat. Methiothepin (100 micrograms kg-1) caused an initial, unsustained blockade of evoked depressor responses whilst ketanserin (100 micrograms kg-1) was without effect. By comparison, ondansetron dose dependently inhibited evoked depressor responses and was maximally active at 100 micrograms kg-1, causing a 57.5 +/- 0.9% reduction. An ID50 value of 36.7 micrograms kg-1 was estimated by regression analysis. In contrast, granisetron caused complete blockade of the depressor response with an ID50 of 0.4 microgram kg-1. Bell-shaped dose-effect curves were demonstrated for both granisetron and ondansetron. Intrathecal dosing with granisetron (100 ng) into the thoracolumbar region of the spinal cord prevented the depressor response to colo-rectal distension, suggesting a spinal site of action. The pseudoaffective depressor responses were not facilitated by pre-dosing with the 5-HT receptor agonists, 8-OH DPAT, alpha-methyltryptamine or 1-phenyl-biguanide. However, 8-OH DPAT (100 micrograms kg-1) facilitated pressor responses. It is suggested that 5-HT3-like receptors may have a role in modulating depressor responses to visceral pain and that in this action different 5-HT3 receptor antagonists are not necessarily equi-effective.
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PMID:5-Hydroxytryptamine3 receptor antagonism modulates a noxious visceral pseudoaffective reflex. 763 Apr 81

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

The use of high doses of cisplatin in treating cancers has been limited by two major adverse effects--emesis and peripheral neuropathies. The emesis has become largely controlled by the introduction of a new class of drugs--the 5-HT3 receptor antagonists. The current study was undertaken to determine if these drugs would also prevent cisplatin-induced neuropathy. We have used a developing rat as an animal model and determined the effects of cisplatin on morphology (loss of spinal cord calcitonin gene-related peptide (CGRP)-containing neurons) and behavior (gait abnormalities and pain perception). Rat pups from the age of 5 days were treated twice weekly for 4 weeks with cisplatin (1 mg/kg), the 5-HT3 antagonist MDL 72222 (3 mg/kg) or both. The animals were tested for pain perception (using tail-flick latencies) at 17 and 21 days of age and for a gait abnormality at 24 days of age. At 34 days of age, the animals were perfused and the lumbar region of the spinal cords stained immunocytochemically for CGRP. Our results show that cisplatin treatment resulted in a dramatic loss of CGRP neurons in the dorsal horn of the spinal cord and a corresponding increase in the animals' threshold for pain. In addition, the animals showed a pronounced gait abnormality, characterized by 'toeing-in'. Treatment with MDL 72222 not only failed to protect against the loss of CGRP neurons but also worsened the gait abnormalities seen after cisplatin treatment alone. These studies confirm and extend the list of morphological and functional adverse effects of cisplatin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A 5-HT3 receptor antagonist fails to prevent cisplatin-induced toxicity in immature rat spinal cord. 779 48

5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptors on primary afferent nociceptive neurones in the spinal cord dorsal horn. Therefore, ondansetron (a 5-HT3 receptor antagonist) may increase the perception of a noxious stimulus or decrease the effects of concurrently administered antinociceptive drugs. Using a randomized, double-blind, crossover study design, we have tested this hypothesis in eight healthy volunteers who, on three different days, received either ondansetron and placebo, ondansetron and alfentanil or placebo and alfentanil. Experimental pain was induced with heat, cold, mechanical pressure and electrical stimulation. Ondansetron alone did not change the response to any of the experimental tests, but alfentanil and the combination ondansetron-alfentanil significantly changed the response compared with ondansetron alone. There was no difference between alfentanil alone and the combination ondansetron-alfentanil. We conclude that ondansetron does not change the response to pressure, heat, cold or electrical nociceptive stimuli or antagonize the analgesic effect of alfentanil.
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PMID:Ondansetron does not inhibit the analgesic effect of alfentanil. 794 58

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

There has been tremendous interest in 5-HT3 receptor antagonists since their discovery and the subsequent identification of 5-HT3 receptors in the CNS. Based on the results of early behavioural tests with these compounds, there has been substantial interest in their potential use for the treatment of various CNS disorders. In this review, Andrew Greenshaw attempts to clarify the status of the therapeutic potential of these drugs, discussing inconsistencies in preclinical findings and identifying areas in need of clarification through future research. 5-HT3 receptor antagonists are claimed to be potentially useful in the treatment of nausea, inflammatory pain (migraine and irritable bowel syndrome), anxiety, depression, schizophrenia, dementia and drug abuse!
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PMID:Behavioural pharmacology of 5-HT3 receptor antagonists: a critical update on therapeutic potential. 810 96

A series of aryl tropanyl esters and amides related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester (ICS 205930, CAS 89565-68-4) were synthesized and evaluated for antinociceptive activity using the hot-plate test. Of these, the benzofurane-3-carboxylic ester of tropine (1) was found powerfully to increase the pain threshold, with a cholinergic mechanism of action. Despite the structural similarity with ICS 205930, the analgesia induced by 1 seems not to be due to 5-HT3 receptor interaction, and there is evidence of involvement of the central 5-HT4 receptor.
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PMID:Synthesis and biological activity of a series of aryl tropanyl esters and amides chemically related to 1H-indole-3-carboxylic acid endo 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ester. Development of a 5-HT4 agonist endowed with potent antinociceptive activity. 821 52


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