Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-HT7 receptor (5-HT7R) is a promising target for the treatment of depression and neuropathic pain. 5-HT7R antagonists exhibited antidepressant effects, while the agonists produced strong anti-hyperalgesic effects. In our efforts to discover selective 5-HT7R antagonists or agonists, N-biphenylylmethyl 2-methoxyphenylpiperazinylalkanamides 1 were designed, synthesized, and biologically evaluated against 5-HT7R. Among the synthesized compounds, N-2'-chlorobiphenylylmethyl 2-methoxyphenylpiperazinylpentanamide 1-8 showed the best binding affinity with a Ki value of 8.69nM and it was verified as a novel antagonist according to functional assays. The compound 1-8 was very selective over 5-HT1DR, 5-HT2AR, 5-HT3R, 5-HT5AR and 5-HT6R and moderately selective over 5-HT1AR, 5-HT1BR and 5-HT2CR. The novel 5-HT7R antagonist 1-8 exhibited an antidepressant effect at a dose of 25mg/kg in the forced swimming test in mice and showed a U-shaped dose-response curve which typically appears in 5-HT7R antagonists such as SB-269970 and lurasidone.
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PMID:Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R antagonists for the treatment of depression. 2512 61

Objective Gender differences, including differences in the prevalence, subtypes and the effectiveness of treatment, are generally recognized in irritable bowel syndrome (IBS). Although serotonin type 3 receptor (5-HT3R) antagonists appear to be more effective in women with diarrhea predominant IBS (IBS-D) than they are in men, the mechanisms underlying these effects remain unclear. The aim of the present was to investigate the gender differences in 5-HT signaling. Methods The subjects were selected from outpatients with IBS-D and healthy controls. Their rectal mucosal S100A, tryptophan hydroxylase (TPH) and 5-HT transporter (5-HTT, SERT, SLC6A4) mRNA expression levels were measured. Clinical symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS) and the self-rating depression scale (SDS). Results The study population of 100 subjects included 47 IBS-D patients and 53 age- and gender-matched healthy controls. The S100A9 (5.20 vs. 1.90, p=0.001) and SLC6A4 (2.00 vs. 1.00, p=0.019) mRNA levels in the rectal mucosa of women with IBS-D were significantly higher than those in men. Among the healthy controls, the S100A10 expression levels in men were higher than those in women (1.33 vs. 0.82, p=0.005). The S100A8 and S100A10 expression levels in women with IBS-D were positively correlated with their diarrhea scores (r=0.55 and 0.58, p<0.05). Conclusion 5-HT signaling might be a major contributor to the symptoms of IBS in men, and the differences may be associated with the effectiveness of 5-HT3R antagonists.
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PMID:Gender Differences in Serotonin Signaling in Patients with Diarrhea-predominant Irritable Bowel Syndrome. 2845 30