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)

Zatosetron (13 mg or 0.19 mg/kg), a potent and selective 5-HT3 receptor antagonist was studied with a 30 min infusion in a crossover double-blind placebo-controlled trial for acute migraine therapy. Groups receiving zatosetron and placebo were demographically similar and zatosetron was well-tolerated in all patients with no clinically significant adverse effects. Migraine severity was reduced in both the placebo and zatosetron groups with no statistically significant differences between zatosetron and placebo. Likewise, no statistically significant differences between placebo and zatosetron treatment groups were identified with regard to migraine duration, overall migraine severity or the relief medication required. Although several limitations of this study exist, these data documenting a lack of benefit of intravenously-administered zatosetron in alleviating the acute pain of migraine add to the list of 5-HT3 receptor antagonists that have failed to support efficacy of this therapeutic modality in the acute treatment of migraine.
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PMID:Zatosetron, a 5-HT3 receptor antagonist in a multicenter trial for acute migraine. 798 90

Long-term potentiation (LTP), a use dependent long-lasting modification of synaptic strength, was first discovered in the hippocampus and later shown to occur in sensory areas of the spinal cord. Here we demonstrate that spinal LTP requires the activation of a subset of superficial spinal dorsal horn neurons expressing the neurokinin-1 receptor (NK1-R) that have previously been shown to mediate certain forms of hyperalgesia. These neurons participate in local spinal sensory processing, but are also the origin of a spino-bulbo-spinal loop driving a 5-hydroxytryptamine 3 receptor (5HT3-R)- mediated descending facilitation of spinal pain processing. Using a saporin-substance P conjugate to produce site-specific neuronal ablation, we demonstrate that NK1-R expressing cells in the superficial dorsal horn are crucial for the generation of LTP-like changes in neuronal excitability in deep dorsal horn neurons and this is modulated by descending 5HT3-R-mediated facilitatory controls. Hippocampal LTP is associated with early expression of the immediate-early gene zif268 and knockout of the gene leads to deficits in long-term LTP and learning and memory. We found that spinal LTP is also correlated with increased neuronal expression of zif268 in the superficial dorsal horn and that zif268 antisense treatment resulted in deficits in the long-term maintenance of inflammatory hyperalgesia. Our results support the suggestion that the generation of LTP in dorsal horn neurons following peripheral injury may be one mechanism whereby acute pain can be transformed into a long-term pain state.
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PMID:Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. 1693 Apr 6

This study assesses the antinociceptive effect induced by different dosages of topiramate (TP), an anticonvulsant drug that is orally administered in models of neuropathic pain and acute pain in rats and mice, respectively. Orally administered TP (80 mg/Kg) in mice causes antinociception in the first and second phases of a formalin test, while in doses of 20 and 40 mg/Kg it was only effective in the second phase. TP (80 mg/Kg, p.o) also exhibited antinociceptive action in the hot plate test, however, it did not have an effect in the capsaicin test in mice, nor in the model of neuropathic pain in diabetic rats. The antinociceptive effect caused by TP (80 mg/Kg, p.o) in the formalin test was reversed by prior treatment with naloxone (opioid antagonist), but not with glibenclamide (antagonist of the potassium channel), ondansetron (antagonist of the serotonin 5HT3 receptor) or cyproheptadine (antagonist of the serotonin 5HT2A receptor).The data show that TP has an important antinociceptive effect in the models of nociception induced by chemical (formalin) or thermal (hot plate) stimuli, and that the opioid system plays a part in the antinociceptive effect, as shown by formalin.
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PMID:Antinociceptive effect of topiramate in models of acute pain and diabetic neuropathy in rodents. 1905 4