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)

Effects of the non-selective 5-hydroxytryptamine (5-HT) receptor agonist m-chlorophenylpiperazine (m-CPP) on the nociceptive responsiveness in a hot plate and tail flick tests were examined in mice. Intraperitoneal administration of m-CPP (1-10 mg/kg) produced a dose-dependent antinociception in both those tests; the effect of m-CPP in the hot plate test was stronger. The antinociceptive effect of m-CPP in either test was abolished by pretreatment with mesulergine (2 mg/kg), ritanserin (1-2 mg/kg), 5-HT2A/5-HT2C receptor antagonists, and metergoline (0.5-2 mg/kg), a non-selective 5-HT receptor antagonist. On the other hand, spiperone (0.25-0.5 mg/kg), a dopamine, 5-HT1A and 5-HT2A receptor antagonist; pindolol (4-8 mg/kg), a beta-adrenoceptor, 5-HT1A and 5-HT1B receptor antagonist and zacopride (0.1-1 mg/kg) a 5-HT3 receptor antagonist, did not affect the analgesia induced by m-CPP. Neither of the drugs used as putative receptor antagonists changed the nociceptive responsiveness in mice. The obtained results suggest that the analgesia induced by m-CPP is mediated by 5-HT2C receptors.
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PMID:Involvement of 5-HT2C receptors in the m-CPP-induced antinociception in mice. 789 29

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

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

Besides the important role of emotional factors in the production of psychological-stress-induced analgesia (PSY-SIA), recent attention to the participation of serotonergic (5-HTnergic) neurons in the fear- and anxiety-evoking mechanism led us to examine the effects of 5-HTnergic ligands on PSY-SIA. Pretreatment of mice with 2.0 to 10 mg/kg of methysergide, a 5-HT receptor antagonist, or 1.0 to 10 mg/kg of buspirone, a 5-HT1A receptor partial agonist, dose-dependently suppressed the production of PSY-SIA. Ritanserin, a 5-HT2 receptor antagonist, 1.0 to 5.0 mg/kg, or Y-25,130, a 5-HT3 receptor antagonist, 0.03 and 0.1 mg/kg, also inhibited PSY-SIA dose-dependently, while (+/-)pindolol, a 5-HT1A/1B receptor antagonist, was ineffective at doses up to 3.0 mg/kg. Furthermore, the suppressive effect of PSY-stress on the development of antinociceptive tolerance to morphine was also antagonized by methysergide, buspirone, ritanserin and Y-25,130, but not by (+/-)pindolol. These results suggest that 5-HT receptor (5-HT1A, 5-HT2 and 5-HT3 but not 5-HT1B)-mediated mechanisms play an important role in the production of PSY-SIA.
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PMID:Involvement of serotonergic receptor subtypes in the production of antinociception by psychological stress in mice. 848 1

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 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 spinal cord contains endogenous substances (such as cholecystokinin, FMRFamide, etc.) that can block the analgesic effects of opiates. Anti-opiate actions have been most commonly studied by exogenous administration of receptor agonists and receptor antagonists of these substances. However, we have recently demonstrated that anti-analgesia can be brought under environmental control through Pavlovian conditioning. Whereas analgesia can be conditioned to signals for danger, anti-analgesia can be conditioned to signals for safety. Using this paradigm, we have previously demonstrated that conditioned anti-analgesia can reverse a variety of opiate analgesic states, including those produced by conditioned danger signals, systemic morphine, and intrathecal mu- and delta-opiate receptor agonists. These data raise the question of the generality of anti-analgesia actions. The present series of experiments examined the ability of conditioned anti-analgesia to affect non-opiate analgesic states induced by spinal delivery of GABA(A), GABA(B), 5HT2 + 5HT1, and 5HT3 receptor agonists. While conditioned anti-analgesia had no effect on GABA(A) or 5HT2 + 5HT1 non-opiate analgesias, conditioned anti-analgesia completely blocked GABA(B) and 5HT3 non-opiate analgesias. These findings clearly demonstrate that conditioned anti-analgesia can powerfully modulate non-opiate as well as opiate analgesias and bring into question whether putative anti-opiate neuroactive substances may have broader actions than previously suggested.
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PMID:Reversal of spinal cord non-opiate analgesia by conditioned anti-analgesia in the rat. 923 66

1. In this investigation, the influence of a selective 5HT3 antagonist, granisetron, on morphine-induced antinociception in the formalin test has been studied. There is evidence that the 5HT3 receptor system takes part in analgesic response. 2. Male albino mice weighing 22-27 g were used in the experiments. All drugs were administered 30 min before formalin injection. Comparison between groups was made by analysis of variance and then Newman-Keuls test. 3. Different doses of morphine (1.5-9.0 mg/kg) subcutaneously induced antinociception in both phases of the formalin test. 4. Coadministration of granisetron (0.1-10.0 mg/kg) intraperitoneally had no effect on morphine analgesia, but granisetron injection alone induced dose-dependent analgesia in both phases of the formalin test. 5. Results of this study suggest a role for a new selective 5HT3 antagonist in analgesia.
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PMID:Effect of granisetron on morphine-induced analgesia in mice by formalin test. 959 79

1. The in vitro hemisected spinal cord from young rat was used to investigate the mechanism of serotoninergic modulation of primary afferent-mediated synaptic transmission in the dorsal horn through activation of the 5-HT3 receptor. 2. Dorsal root-evoked excitatory post-synaptic potentials (DR-EPSPs) were recorded intracellularly from dorsal horn neurones. Extracellular recordings of the population primary afferent depolarization (PAD) and the dorsal root-evoked dorsal root reflex (DR-DRR) were made from segmental dorsal roots. 3. 5-Hydroxytryptamine (5-HT) and the selective 5-HT3 receptor agonist 1-(m-chloro-phenyl)-biguanide hydrochloride (m-ChPB) (10 and 50 microM) induced statistically significant reductions of the DR-EPSP amplitude (P<0.001) and duration (P<0.001) in the majority of dorsal horn neurones. The 5-HT3 receptor selective antagonists 3-Tropanyl-indole-3-carboxylate hydrochloride (Tropisetron, 10 microM) and N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1 ,4-benzoxazine-8-carboxamide (Y-25130, 10 microM) abolished m-ChPB-induced DR-EPSP attenuation and partially blocked the 5-HT effect. 4. m-ChPB (50 microM)-induced DR-EPSP amplitude and duration attenuation was retained in the presence of the GABA(A) receptor antagonist bicuculline (30 microM), the GABA(B) receptor antagonist saclofen (50 microM) and the opioid receptor antagonist naloxone (50 microM). 5. Both 5-HT and m-ChPB (10 and 50 microM) induced a PAD but the mean peak amplitude of 5-HT-induced PAD was significantly greater than PAD to m-ChPB (98.6+/-12 microV compared to 51.8+/-10 V for 50 microM of agonist, respectively). Tropisetron partially reduced 5-HT-induced PAD and abolished m-ChPB-induced PAD. 5-HT, but not m-ChPB, significantly (P<0.001) reduced the peak amplitude of the DR-DRR and this action of 5-HT was unaffected by Tropisetron or Y-25130. 6. These data provide experimental evidence for a putative cellular mechanism at the level of the dorsal horn for anti-nociceptive effects of 5-HT3 receptor activation. This 5-HT3-mediated modulation of sensory afferent transmission was evidently independent of inhibitory GABA- or opioid-dependent interneuronal pathways. The extent to which the 5-HT3 receptor could be involved in the operation of endogenous analgesia and sensory modulation by descending monoamine bulbo-spinal pathways is discussed.
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PMID:Modulation of afferent-evoked neurotransmission by 5-HT3 receptors in young rat dorsal horn neurones in vitro: a putative mechanism of 5-HT3 induced anti-nociception. 1043 90


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