Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of nociceptin on the exploratory behavior of mice were examined using an automatic hole-board apparatus. A low dose of nociceptin (0.01 nmol, i.c.v.) had an anxiolytic effect, as reflected by an increase in head-dipping behavior. However, high doses of nociceptin (1-5 nmol, i.c.v.) produced a dose-dependent anxiogenic effect, as reflected by a decrease in head-dipping behavior. Both the anxiolytic and anxiogenic effects of nociceptin were antagonized by nocistatin, an opioid receptor-like 1 (ORL1) receptor antagonist. Although a low dose (0.01 nmol, i.c.v.) of nociceptin significantly increased the rate of serotonin (5-hyroxytryptamine, 5-HT) turnover in the hippocampus, a high dose (5 nmol, i.c.v.) of nociceptin significantly decreased this turnover in the amygdala. Furthermore, the anxiolytic effect of nociceptin at a low dose was antagonized by N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide 3HCl (WAY100635), a 5-HT1A receptor antagonist. On the other hand, the anxiogenic effect of nociceptin at a high dose was antagonized by R(+)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist. In conclusion, the results of this study suggest that nociceptin has dose-related anxiolytic and anxiogenic effects as a result of the activation of ORL1 receptors. The present results also suggest that a low dose of nociceptin has an anxiolytic effect via the activation of 5-HT ergic function in the hippocampus, while a high dose of nociceptin has an anxiogenic effect via the inhibition of 5-HT ergic function in the amygdala.
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PMID:Effects of nociceptin on the exploratory behavior of mice in the hole-board test. 1506 58

Understanding mechanism of neuropathic pain is too complex and involves both peripheral and central pathophysiological phenomenon. Accordingly the treatment of neuropathic pain is also very complex and is unsatisfactory. The present review attempts to discuss the currently employed pharmacological agents for the management of neuropathic pain including anti-depressants, anti-convulsants, NMDA receptor antagonists, topical & local anesthetics, and upload analgesics. However, the existing pharmacotherapy has marginal efficacy and significant side effects. The review also gives an insight into various pharmacological agents with potential neuropathic pain attenuating properties in experimental models that include NSAIDs, corticosteroids, ion channel blockers (Ca(2+), Na(+), K(+), and TRP channel); ion exchange modulators (NCE and NHE); ion/molecule transport modulators (NKCC-1 and glycine); receptor modulators (kinin, histamine, 5-HT1A, dopamine, alpha & beta adrenergic, purinergic, excitatory amino acid, sigma, ORL1, endothelin, melanocortin, ephrin and PAR); enzyme inhibitors (cytosolic kinase, metalloproteinase, protease, vasopeptidase, D-amino acid oxidase, fatty acid amide hydrolase, aldose reductase and sorbitol dehydrogenase); other ligands (AGE, RAGEs, neuropeptides, neurotrophic factor, complement cascade, cytokine, glial cell & gap junction, nitrous oxide, growth factor, cell adhesion molecule and neuronal sprouting molecule). Moreover, some advanced therapeutic approaches such as neuronal cell transplantation, stem cell therapy, anti-sense oligonucleotide and recombinant therapy have also been dicussed.
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PMID:Drug therapy of neuropathic pain: current developments and future perspectives. 2409 49