Effects of the selective 5-HT7 receptor antagonist SB-269970 in animal models of psychosis and cognition

Waters, Kerry; Stean, Tania O.; Hammond, Beverley; Virley, David; Upton, Neil; Kew, James N.C.; Hussain, Ishrut

doi:10.1016/j.bbr.2011.12.009

Cited by 53 publications

(42 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32,33 This appears to be highly important because depressive disorders are often accompanied by cognitive decline. Thus pro-cognitive properties may have some benefit in regard to the treatment of depression.…”

Section: Resultsmentioning

confidence: 99%

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT₇ receptor antagonists and their psychotropic properties

et al. 2015

View full text Add to dashboard Cite

A series of alkyl/arylsulfonamide derivatives of (aryloxy)ethylpiperidines as highly potent 5-HT 7 receptor antagonists has been developed through structure-based design on the previously identified compound PZ-766. This resulted in highly potent antagonist 10 Ĳ3-fluoro-N-Ĳ1-{2-ĳ(propan-2-yl)phenoxy]ethyl}-piperidin-4-yl)-benzenesulfonamide) which was more active in vivo than PZ-766 and SB-269970 in forced swim test in mice (MED = 2.5 mg kg −1 ), and displayed comparable effects to SB-269970 in four-plate test in mice (MED = 1.25 mg kg −1 ) and novel object recognition test in rats (MED = 1 mg kg −1 ). The results highlight the antidepressant, anxiolytic and pro-cognitive potential of the arylsulfonamide derivatives of (aryloxy)ethylpiperidines with 5-HT 7 receptor antagonist properties and warrant further studies to explore their therapeutic potential for the treatment of CNS disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT₇ receptor antagonists and their psychotropic properties

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In the gut, studies have shown that 5-HT induces muscle relaxation by affecting 5-HT 7 receptors on smooth muscle cells in addition to neuronal 5-HT 7 receptors (55)(56)(57)(58). Although the effects of selective 5-HT 7 antagonism have been studied in several animal behavioral models where it has been shown to have anxiolytic (59-61), antidepressant (62)(63)(64), and antipsychotic-like effects (65,66), to our knowledge, no current data are available on the effects of 5-HT 7 receptor antagonists in IBD.…”

Section: Cd11cmentioning

confidence: 99%

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Kim

Bridle

Ghia

et al. 2013

The Journal of Immunology

114

View full text Add to dashboard Cite

Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7 (5-HT7) receptor is one of the most recently identified members of the 5-HT receptor family, and dendritic cells express this receptor. In this study, we investigated the effect of blocking 5-HT7 receptor signaling in experimental colitis with a view to develop an improved therapeutic strategy in intestinal inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7−/−) and irradiated wild-type mice reconstituted with bone marrow cells harvested from 5-HT7−/− mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted in lower clinical disease, histological damage, and proinflammatory cytokine levels compared with vehicle-treated mice post-DSS. Colitis severity was significantly lower in 5-HT7−/− mice and in mice reconstituted with bone marrow cells from 5-HT7−/− mice compared with control mice after DSS colitis. 5-HT7−/− mice also had significantly reduced DNBS-induced colitis. These observations provide us with novel information on the critical role of the 5-HT7 receptor in immune response and inflammation in the gut, and highlight the potential benefit of targeting this receptor to alleviate the severity of intestinal inflammatory disorders such as inflammatory bowel disease.

show abstract

“…Recently, 5-HT7R has been found to play important roles in circadian rhythm [10,11], sleep [12,13], body temperature regulation [14], and neurological development of the hippocampus and prefrontal cortex [15,16,17]. In addition, in the field of psychiatry, its roles in antidepressant and anxiolytic actions [18,19,20], memory, and learning have been demonstrated in animal models [21,22,23,24,25,26]. Several lines of evidence suggest that 5-HT7R plays a relevant role in schizophrenia pathogenesis and treatment response.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, a decrease in the expression of the HTR7 gene in the prefrontal cortex has been reported in postmortem brain tissue of patients with schizophrenia [27], and a relationship with sites located near to the HTR7 gene has been reported in genome-wide linkage studies of schizophrenia [28,29]. Based on ethnopharmacological animal studies, it has been hypothesized that 5-HT7R antagonism may be related to the etiology of schizophrenia and may be effective for improving cognitive function [22,23,24,25,26]. Indeed, several second-generation antipsychotic (SGA) drugs, such as amisulpride, clozapine, lurasidone, risperidone, quetiapine, aripiprazole, and perospirone, are known to have a high affinity for 5-HT7R [30,31,32,33].…”

Section: Introductionmentioning

confidence: 99%

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

Takekita

Fabbri²,

Kato³

et al. 2015

Neuropsychobiology

View full text Add to dashboard Cite

Background: Individual differences in serotonin 7 receptor (5-HT7R) may result in variable response to antipsychotics with 5-HT7R antagonism. This study investigated the relationship between single nucleotide polymorphisms (SNPs) in the 5-HT7R gene (HTR7) and the efficacy of second-generation antipsychotic drugs with a high affinity for this receptor in Japanese schizophrenia. Methods: Perospirone or aripiprazole was administered to 100 patients with schizophrenia in a randomized controlled study. All patients were genotyped for three candidate SNPs (rs12412496, rs7916403, and rs1935349). Patient improvement on the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks was assessed as the primary outcome. PANSS 5-factor scores were investigated as the secondary outcome. Results: Improvement on the PANSS total score and genetic polymorphisms showed no correlation. The rs12412496-rs7916403-rs1935349 A-T-A haplotype was correlated with worse improvement in the cognition score (haplotype frequency: 0.285, p = 0.046, permuted p = 0.043). Conclusion: Our results show that HTR7 variants are not related to the overall improvement in schizophrenia symptoms.

show abstract

Effects of the selective 5-HT7 receptor antagonist SB-269970 in animal models of psychosis and cognition

Cited by 53 publications

References 54 publications

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT₇ receptor antagonists and their psychotropic properties

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT₇ receptor antagonists and their psychotropic properties

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

Contact Info

Product

Resources

About

Effects of the selective 5-HT7 receptor antagonist SB-269970 in animal models of psychosis and cognition

Cited by 53 publications

References 54 publications

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT7 receptor antagonists and their psychotropic properties

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT7 receptor antagonists and their psychotropic properties

Targeted Inhibition of Serotonin Type 7 (5-HT7) Receptor Function Modulates Immune Responses and Reduces the Severity of Intestinal Inflammation

Serotonin 7 Receptor Variants Are Not Associated with Response to Second-Generation Antipsychotics in Japanese Schizophrenia Patients

Contact Info

Product

Resources

About

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT₇ receptor antagonists and their psychotropic properties

Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT₇ receptor antagonists and their psychotropic properties