Loading…

The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor

•We establish a system to screen monoamine reuptake inhibitors fast and accurately.•Using this system, we discover a potential antidepressant 071031B.•071031B has robust antidepressant effect in vivo and transporter affinity in vitro.•071031B is expected to be a novel serotonin and noradrenaline reu...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience letters 2013-06, Vol.544, p.68-73
Main Authors: Xue, Rui, Zhang, Yan-Ping, Jin, Zeng-Liang, Yuan, Li, He, Xin-Hua, Zhao, Nan, Chen, Hong-Xia, Zhang, Li-Ming, Fan, Shi-Yong, Zhong, Bo-Hua, Zhang, You-Zhi, Li, Yun-Feng
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33
cites cdi_FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33
container_end_page 73
container_issue
container_start_page 68
container_title Neuroscience letters
container_volume 544
creator Xue, Rui
Zhang, Yan-Ping
Jin, Zeng-Liang
Yuan, Li
He, Xin-Hua
Zhao, Nan
Chen, Hong-Xia
Zhang, Li-Ming
Fan, Shi-Yong
Zhong, Bo-Hua
Zhang, You-Zhi
Li, Yun-Feng
description •We establish a system to screen monoamine reuptake inhibitors fast and accurately.•Using this system, we discover a potential antidepressant 071031B.•071031B has robust antidepressant effect in vivo and transporter affinity in vitro.•071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor. Depression is a severe mood disorder with increasing morbidity and suicidality, while the current therapy is not satisfactory. Serotonin and noradrenaline reuptake inhibitors (SNRIs) have been reported to have higher efficacy and/or faster acting rate than commonly used antidepressants. The present study was designed to screen the potential SNRIs, using in vitro radioligand receptor binding assays and in vivo animal tests, and introduced the discovery of 071031B. In the tail suspension test and forced swimming test in mice, six compounds (071017S, 071026W, 071031A, 071031B, 080307A and 080307B) showed robust antidepressant activity, without stimulant effect on the locomotor activity or other side effects, and the minimal effective dose of 071017S, 071026W, 071031A and 071031B was less than that of duloxetine; in vitro binding tests indicated that 071031B had high affinity to both serotonin transporter and noradrenaline transporter with similar inhibitory rates to duloxetine at 1 and 100nM; acute toxicity test indicated that the LD50 value of 071031B was similar to that of duloxetine. These findings demonstrated that this integrated system, combining high throughput screening technology and in vivo animal tests, is effective to screen potential monoamine reuptake inhibitors fast and accurately; 071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor for its robust antidepressant activity and transporter affinity.
doi_str_mv 10.1016/j.neulet.2013.02.076
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1372054438</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0304394013002851</els_id><sourcerecordid>1372054438</sourcerecordid><originalsourceid>FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33</originalsourceid><addsrcrecordid>eNp9kEFr3DAUhEVJaTab_IMQdMwhdp8ky7IvgWZp08JCe0jPQpaeWW280kayA_n3cXDSY08Phpk3zEfIJYOSAau_7suA04BjyYGJEngJqv5EVqxRvFCt4idkBQKqQrQVnJKznPcAIJmsvpBTLqQCJeoV-fOwQ-p8tvEZ0wuNPQXFQLC7G2pomMWBZkxxjMEHaoKbtWRcwmAGH5AmnI6jeUTqw853fozpnHzuzZDx4v2uyd8f3x82P4vt7_tfm2_bwopWjoV0DciauZ4J0VpmsBHcOFE3rKqZbLFuOVeukl3PGpRouw646nrBe5SNNUKsyfXy95ji04R51Id5BQ6DCRinrJlQHGRViWa2VovVpphzwl4fkz-Y9KIZ6DeWeq8XlvqNpQauZ5Zz7Oq9YeoO6P6FPuDNhtvFgPPOZ49JZ-sxWHQ-oR21i_7_Da9YsYYB</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1372054438</pqid></control><display><type>article</type><title>The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor</title><source>ScienceDirect Freedom Collection 2022-2024</source><creator>Xue, Rui ; Zhang, Yan-Ping ; Jin, Zeng-Liang ; Yuan, Li ; He, Xin-Hua ; Zhao, Nan ; Chen, Hong-Xia ; Zhang, Li-Ming ; Fan, Shi-Yong ; Zhong, Bo-Hua ; Zhang, You-Zhi ; Li, Yun-Feng</creator><creatorcontrib>Xue, Rui ; Zhang, Yan-Ping ; Jin, Zeng-Liang ; Yuan, Li ; He, Xin-Hua ; Zhao, Nan ; Chen, Hong-Xia ; Zhang, Li-Ming ; Fan, Shi-Yong ; Zhong, Bo-Hua ; Zhang, You-Zhi ; Li, Yun-Feng</creatorcontrib><description>•We establish a system to screen monoamine reuptake inhibitors fast and accurately.•Using this system, we discover a potential antidepressant 071031B.•071031B has robust antidepressant effect in vivo and transporter affinity in vitro.•071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor. Depression is a severe mood disorder with increasing morbidity and suicidality, while the current therapy is not satisfactory. Serotonin and noradrenaline reuptake inhibitors (SNRIs) have been reported to have higher efficacy and/or faster acting rate than commonly used antidepressants. The present study was designed to screen the potential SNRIs, using in vitro radioligand receptor binding assays and in vivo animal tests, and introduced the discovery of 071031B. In the tail suspension test and forced swimming test in mice, six compounds (071017S, 071026W, 071031A, 071031B, 080307A and 080307B) showed robust antidepressant activity, without stimulant effect on the locomotor activity or other side effects, and the minimal effective dose of 071017S, 071026W, 071031A and 071031B was less than that of duloxetine; in vitro binding tests indicated that 071031B had high affinity to both serotonin transporter and noradrenaline transporter with similar inhibitory rates to duloxetine at 1 and 100nM; acute toxicity test indicated that the LD50 value of 071031B was similar to that of duloxetine. These findings demonstrated that this integrated system, combining high throughput screening technology and in vivo animal tests, is effective to screen potential monoamine reuptake inhibitors fast and accurately; 071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor for its robust antidepressant activity and transporter affinity.</description><identifier>ISSN: 0304-3940</identifier><identifier>EISSN: 1872-7972</identifier><identifier>DOI: 10.1016/j.neulet.2013.02.076</identifier><identifier>PMID: 23570736</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Acute toxicity ; Animals ; Antidepressants ; Antidepressive Agents - administration &amp; dosage ; Antidepressive Agents - chemistry ; Antidepressive Agents - pharmacokinetics ; Behavior, Animal - drug effects ; Behavioral despair models ; Depression - physiopathology ; Depression - prevention &amp; control ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical - methods ; Dual reuptake inhibitors ; Female ; Integrated evaluation system ; Male ; Mice ; Mice, Inbred ICR ; Monoamine transporters ; Norepinephrine - antagonists &amp; inhibitors ; Serotonin Uptake Inhibitors - administration &amp; dosage ; Serotonin Uptake Inhibitors - pharmacokinetics ; Survival Rate</subject><ispartof>Neuroscience letters, 2013-06, Vol.544, p.68-73</ispartof><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33</citedby><cites>FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23570736$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xue, Rui</creatorcontrib><creatorcontrib>Zhang, Yan-Ping</creatorcontrib><creatorcontrib>Jin, Zeng-Liang</creatorcontrib><creatorcontrib>Yuan, Li</creatorcontrib><creatorcontrib>He, Xin-Hua</creatorcontrib><creatorcontrib>Zhao, Nan</creatorcontrib><creatorcontrib>Chen, Hong-Xia</creatorcontrib><creatorcontrib>Zhang, Li-Ming</creatorcontrib><creatorcontrib>Fan, Shi-Yong</creatorcontrib><creatorcontrib>Zhong, Bo-Hua</creatorcontrib><creatorcontrib>Zhang, You-Zhi</creatorcontrib><creatorcontrib>Li, Yun-Feng</creatorcontrib><title>The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor</title><title>Neuroscience letters</title><addtitle>Neurosci Lett</addtitle><description>•We establish a system to screen monoamine reuptake inhibitors fast and accurately.•Using this system, we discover a potential antidepressant 071031B.•071031B has robust antidepressant effect in vivo and transporter affinity in vitro.•071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor. Depression is a severe mood disorder with increasing morbidity and suicidality, while the current therapy is not satisfactory. Serotonin and noradrenaline reuptake inhibitors (SNRIs) have been reported to have higher efficacy and/or faster acting rate than commonly used antidepressants. The present study was designed to screen the potential SNRIs, using in vitro radioligand receptor binding assays and in vivo animal tests, and introduced the discovery of 071031B. In the tail suspension test and forced swimming test in mice, six compounds (071017S, 071026W, 071031A, 071031B, 080307A and 080307B) showed robust antidepressant activity, without stimulant effect on the locomotor activity or other side effects, and the minimal effective dose of 071017S, 071026W, 071031A and 071031B was less than that of duloxetine; in vitro binding tests indicated that 071031B had high affinity to both serotonin transporter and noradrenaline transporter with similar inhibitory rates to duloxetine at 1 and 100nM; acute toxicity test indicated that the LD50 value of 071031B was similar to that of duloxetine. These findings demonstrated that this integrated system, combining high throughput screening technology and in vivo animal tests, is effective to screen potential monoamine reuptake inhibitors fast and accurately; 071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor for its robust antidepressant activity and transporter affinity.</description><subject>Acute toxicity</subject><subject>Animals</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - administration &amp; dosage</subject><subject>Antidepressive Agents - chemistry</subject><subject>Antidepressive Agents - pharmacokinetics</subject><subject>Behavior, Animal - drug effects</subject><subject>Behavioral despair models</subject><subject>Depression - physiopathology</subject><subject>Depression - prevention &amp; control</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Dual reuptake inhibitors</subject><subject>Female</subject><subject>Integrated evaluation system</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Monoamine transporters</subject><subject>Norepinephrine - antagonists &amp; inhibitors</subject><subject>Serotonin Uptake Inhibitors - administration &amp; dosage</subject><subject>Serotonin Uptake Inhibitors - pharmacokinetics</subject><subject>Survival Rate</subject><issn>0304-3940</issn><issn>1872-7972</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kEFr3DAUhEVJaTab_IMQdMwhdp8ky7IvgWZp08JCe0jPQpaeWW280kayA_n3cXDSY08Phpk3zEfIJYOSAau_7suA04BjyYGJEngJqv5EVqxRvFCt4idkBQKqQrQVnJKznPcAIJmsvpBTLqQCJeoV-fOwQ-p8tvEZ0wuNPQXFQLC7G2pomMWBZkxxjMEHaoKbtWRcwmAGH5AmnI6jeUTqw853fozpnHzuzZDx4v2uyd8f3x82P4vt7_tfm2_bwopWjoV0DciauZ4J0VpmsBHcOFE3rKqZbLFuOVeukl3PGpRouw646nrBe5SNNUKsyfXy95ji04R51Id5BQ6DCRinrJlQHGRViWa2VovVpphzwl4fkz-Y9KIZ6DeWeq8XlvqNpQauZ5Zz7Oq9YeoO6P6FPuDNhtvFgPPOZ49JZ-sxWHQ-oR21i_7_Da9YsYYB</recordid><startdate>20130607</startdate><enddate>20130607</enddate><creator>Xue, Rui</creator><creator>Zhang, Yan-Ping</creator><creator>Jin, Zeng-Liang</creator><creator>Yuan, Li</creator><creator>He, Xin-Hua</creator><creator>Zhao, Nan</creator><creator>Chen, Hong-Xia</creator><creator>Zhang, Li-Ming</creator><creator>Fan, Shi-Yong</creator><creator>Zhong, Bo-Hua</creator><creator>Zhang, You-Zhi</creator><creator>Li, Yun-Feng</creator><general>Elsevier Ireland Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>20130607</creationdate><title>The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor</title><author>Xue, Rui ; Zhang, Yan-Ping ; Jin, Zeng-Liang ; Yuan, Li ; He, Xin-Hua ; Zhao, Nan ; Chen, Hong-Xia ; Zhang, Li-Ming ; Fan, Shi-Yong ; Zhong, Bo-Hua ; Zhang, You-Zhi ; Li, Yun-Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute toxicity</topic><topic>Animals</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - administration &amp; dosage</topic><topic>Antidepressive Agents - chemistry</topic><topic>Antidepressive Agents - pharmacokinetics</topic><topic>Behavior, Animal - drug effects</topic><topic>Behavioral despair models</topic><topic>Depression - physiopathology</topic><topic>Depression - prevention &amp; control</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Dual reuptake inhibitors</topic><topic>Female</topic><topic>Integrated evaluation system</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Monoamine transporters</topic><topic>Norepinephrine - antagonists &amp; inhibitors</topic><topic>Serotonin Uptake Inhibitors - administration &amp; dosage</topic><topic>Serotonin Uptake Inhibitors - pharmacokinetics</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xue, Rui</creatorcontrib><creatorcontrib>Zhang, Yan-Ping</creatorcontrib><creatorcontrib>Jin, Zeng-Liang</creatorcontrib><creatorcontrib>Yuan, Li</creatorcontrib><creatorcontrib>He, Xin-Hua</creatorcontrib><creatorcontrib>Zhao, Nan</creatorcontrib><creatorcontrib>Chen, Hong-Xia</creatorcontrib><creatorcontrib>Zhang, Li-Ming</creatorcontrib><creatorcontrib>Fan, Shi-Yong</creatorcontrib><creatorcontrib>Zhong, Bo-Hua</creatorcontrib><creatorcontrib>Zhang, You-Zhi</creatorcontrib><creatorcontrib>Li, Yun-Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Neuroscience letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xue, Rui</au><au>Zhang, Yan-Ping</au><au>Jin, Zeng-Liang</au><au>Yuan, Li</au><au>He, Xin-Hua</au><au>Zhao, Nan</au><au>Chen, Hong-Xia</au><au>Zhang, Li-Ming</au><au>Fan, Shi-Yong</au><au>Zhong, Bo-Hua</au><au>Zhang, You-Zhi</au><au>Li, Yun-Feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor</atitle><jtitle>Neuroscience letters</jtitle><addtitle>Neurosci Lett</addtitle><date>2013-06-07</date><risdate>2013</risdate><volume>544</volume><spage>68</spage><epage>73</epage><pages>68-73</pages><issn>0304-3940</issn><eissn>1872-7972</eissn><abstract>•We establish a system to screen monoamine reuptake inhibitors fast and accurately.•Using this system, we discover a potential antidepressant 071031B.•071031B has robust antidepressant effect in vivo and transporter affinity in vitro.•071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor. Depression is a severe mood disorder with increasing morbidity and suicidality, while the current therapy is not satisfactory. Serotonin and noradrenaline reuptake inhibitors (SNRIs) have been reported to have higher efficacy and/or faster acting rate than commonly used antidepressants. The present study was designed to screen the potential SNRIs, using in vitro radioligand receptor binding assays and in vivo animal tests, and introduced the discovery of 071031B. In the tail suspension test and forced swimming test in mice, six compounds (071017S, 071026W, 071031A, 071031B, 080307A and 080307B) showed robust antidepressant activity, without stimulant effect on the locomotor activity or other side effects, and the minimal effective dose of 071017S, 071026W, 071031A and 071031B was less than that of duloxetine; in vitro binding tests indicated that 071031B had high affinity to both serotonin transporter and noradrenaline transporter with similar inhibitory rates to duloxetine at 1 and 100nM; acute toxicity test indicated that the LD50 value of 071031B was similar to that of duloxetine. These findings demonstrated that this integrated system, combining high throughput screening technology and in vivo animal tests, is effective to screen potential monoamine reuptake inhibitors fast and accurately; 071031B is expected to be a novel serotonin and noradrenaline reuptake inhibitor for its robust antidepressant activity and transporter affinity.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>23570736</pmid><doi>10.1016/j.neulet.2013.02.076</doi><tpages>6</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0304-3940
ispartof Neuroscience letters, 2013-06, Vol.544, p.68-73
issn 0304-3940
1872-7972
language eng
recordid cdi_proquest_miscellaneous_1372054438
source ScienceDirect Freedom Collection 2022-2024
subjects Acute toxicity
Animals
Antidepressants
Antidepressive Agents - administration & dosage
Antidepressive Agents - chemistry
Antidepressive Agents - pharmacokinetics
Behavior, Animal - drug effects
Behavioral despair models
Depression - physiopathology
Depression - prevention & control
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical - methods
Dual reuptake inhibitors
Female
Integrated evaluation system
Male
Mice
Mice, Inbred ICR
Monoamine transporters
Norepinephrine - antagonists & inhibitors
Serotonin Uptake Inhibitors - administration & dosage
Serotonin Uptake Inhibitors - pharmacokinetics
Survival Rate
title The discovery of 071031B, a novel serotonin and noradrenaline reuptake inhibitor
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T08%3A36%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20discovery%20of%20071031B,%20a%20novel%20serotonin%20and%20noradrenaline%20reuptake%20inhibitor&rft.jtitle=Neuroscience%20letters&rft.au=Xue,%20Rui&rft.date=2013-06-07&rft.volume=544&rft.spage=68&rft.epage=73&rft.pages=68-73&rft.issn=0304-3940&rft.eissn=1872-7972&rft_id=info:doi/10.1016/j.neulet.2013.02.076&rft_dat=%3Cproquest_cross%3E1372054438%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c395t-5d80561df1339c1ae832ad368146159e69227d45bf18e5ecbb027bf32fe58ca33%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1372054438&rft_id=info:pmid/23570736&rfr_iscdi=true