Agonist-like character of the (R)-enantiomer of 1-hydroxy-3-amino-pyrrolid-2-one (HA-966)
HA-966 (1-hydroxy-3-amino-pyrrolid-2-one), an antagonist at the strychine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, only partially inhibits the binding of noncompetitive antagonists to the NMDA receptor but enhances the binding of the NMDA competitive antagonist C...
Gespeichert in:
| Veröffentlicht in: | European journal of pharmacology 1991-09, Vol.208 (1), p.25-29 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 29 |
|---|---|
| container_issue | 1 |
| container_start_page | 25 |
| container_title | European journal of pharmacology |
| container_volume | 208 |
| creator | Pullan, Linda M. Verticelli, Adeline M. Paschetto, Katherine A. |
| description | HA-966 (1-hydroxy-3-amino-pyrrolid-2-one), an antagonist at the strychine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, only partially inhibits the binding of noncompetitive antagonists to the NMDA receptor but enhances the binding of the NMDA competitive antagonist CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid). Here we report that the IC
50 of the active (R)-enantiomer of HA-966 for displacement of [
3H]glycine binding is decreased in the presence of spermine, suggesting that spermine increases the affinity of (R)-HA-966 at the [
3H]glycine site. The IC
50 values of the agonist glycine and the partial agonist 1-aminocyclopropane-1-carboxyalate are also decreases. The IC
50 values of glycine antagonists, 6,7-dinitroquinoxalin-2,3-dione and 7-chlorokynurenic acid are not significantly altered. The spermine shift represents the first demonstration of the agonist-like character of the (R)-enantiomer of HA-966 at the glycine site. |
| doi_str_mv | 10.1016/0922-4106(91)90047-L |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72442614</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>092241069190047L</els_id><sourcerecordid>16115807</sourcerecordid><originalsourceid>FETCH-LOGICAL-c417t-7a76ce1a48c0ba8452d2efa2ee2288935eb0c7b9aaf20876c2ed01556ab66ee03</originalsourceid><addsrcrecordid>eNqFkMGK1EAQhvugrOvqGyjMQWTn0FrV6XTSF2FY1BUGBNGDp6bSqTitSXrszizO25sxw3rTU8Ff318UnxDPEF4hoHkNVimpEcy1xbUF0JXcPhCX9_Ej8Tjn7wBg0eoLcYF1oXVVXIqvm29xDHmSffjBK7-jRH7itIrdatrx6vrTWvJI4xTisKQod8c2xV9HWUgawhjl_phS7EMrlYzjXLndSGvM-ol42FGf-el5Xokv795-vrmV24_vP9xsttJrrCZZUWU8I-naQ0O1LlWruCPFrFRd26LkBnzVWKJOQT2zilvAsjTUGMMMxZV4udzdp_jzwHlyQ8ie-55GjofsKqW1Mqj_C6JBLGuoZlAvoE8x58Sd26cwUDo6BHfS7U5e3cmrs-j-6Hbbufb8fP_QDNz-LS2u5_2L856yp75LNPqQ7zFt6xK0nbE3C8aztLvAyWUfePTchsR-cm0M__7jN21wmyM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>16115807</pqid></control><display><type>article</type><title>Agonist-like character of the (R)-enantiomer of 1-hydroxy-3-amino-pyrrolid-2-one (HA-966)</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>Alma/SFX Local Collection</source><creator>Pullan, Linda M. ; Verticelli, Adeline M. ; Paschetto, Katherine A.</creator><creatorcontrib>Pullan, Linda M. ; Verticelli, Adeline M. ; Paschetto, Katherine A.</creatorcontrib><description>HA-966 (1-hydroxy-3-amino-pyrrolid-2-one), an antagonist at the strychine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, only partially inhibits the binding of noncompetitive antagonists to the NMDA receptor but enhances the binding of the NMDA competitive antagonist CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid). Here we report that the IC
50 of the active (R)-enantiomer of HA-966 for displacement of [
3H]glycine binding is decreased in the presence of spermine, suggesting that spermine increases the affinity of (R)-HA-966 at the [
3H]glycine site. The IC
50 values of the agonist glycine and the partial agonist 1-aminocyclopropane-1-carboxyalate are also decreases. The IC
50 values of glycine antagonists, 6,7-dinitroquinoxalin-2,3-dione and 7-chlorokynurenic acid are not significantly altered. The spermine shift represents the first demonstration of the agonist-like character of the (R)-enantiomer of HA-966 at the glycine site.</description><identifier>ISSN: 0922-4106</identifier><identifier>ISSN: 0014-2999</identifier><identifier>DOI: 10.1016/0922-4106(91)90047-L</identifier><identifier>PMID: 1834473</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>1-Hydroxy-3-amino-pyrrolid-2-one (HA-966) ; Amino Acids - pharmacology ; Amino Acids, Cyclic ; Animals ; Binding, Competitive ; Biological and medical sciences ; brain ; Dose-Response Relationship, Drug ; Excitatory amino acids ; Glycine ; Glycine - chemistry ; Glycine - metabolism ; hydroxy-3-amino-pyrrolid-2-one ; Kynurenic Acid - analogs & derivatives ; Kynurenic Acid - pharmacology ; Male ; Medical sciences ; Miscellaneous ; N-Methyl-D-aspartate (NMDA) ; Neuropharmacology ; Neurotransmitters. Neurotransmission. Receptors ; Pharmacology. Drug treatments ; Polyamines ; Pyrrolidinones - chemistry ; Pyrrolidinones - pharmacology ; Quinoxalines - pharmacology ; Rats ; Rats, Inbred Strains ; Receptors, N-Methyl-D-Aspartate - drug effects ; Receptors, N-Methyl-D-Aspartate - metabolism ; Spermine ; Spermine - pharmacology ; Stereoisomerism ; Synaptosomes - drug effects ; Synaptosomes - metabolism</subject><ispartof>European journal of pharmacology, 1991-09, Vol.208 (1), p.25-29</ispartof><rights>1991</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-7a76ce1a48c0ba8452d2efa2ee2288935eb0c7b9aaf20876c2ed01556ab66ee03</citedby><cites>FETCH-LOGICAL-c417t-7a76ce1a48c0ba8452d2efa2ee2288935eb0c7b9aaf20876c2ed01556ab66ee03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4985049$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1834473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pullan, Linda M.</creatorcontrib><creatorcontrib>Verticelli, Adeline M.</creatorcontrib><creatorcontrib>Paschetto, Katherine A.</creatorcontrib><title>Agonist-like character of the (R)-enantiomer of 1-hydroxy-3-amino-pyrrolid-2-one (HA-966)</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>HA-966 (1-hydroxy-3-amino-pyrrolid-2-one), an antagonist at the strychine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, only partially inhibits the binding of noncompetitive antagonists to the NMDA receptor but enhances the binding of the NMDA competitive antagonist CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid). Here we report that the IC
50 of the active (R)-enantiomer of HA-966 for displacement of [
3H]glycine binding is decreased in the presence of spermine, suggesting that spermine increases the affinity of (R)-HA-966 at the [
3H]glycine site. The IC
50 values of the agonist glycine and the partial agonist 1-aminocyclopropane-1-carboxyalate are also decreases. The IC
50 values of glycine antagonists, 6,7-dinitroquinoxalin-2,3-dione and 7-chlorokynurenic acid are not significantly altered. The spermine shift represents the first demonstration of the agonist-like character of the (R)-enantiomer of HA-966 at the glycine site.</description><subject>1-Hydroxy-3-amino-pyrrolid-2-one (HA-966)</subject><subject>Amino Acids - pharmacology</subject><subject>Amino Acids, Cyclic</subject><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biological and medical sciences</subject><subject>brain</subject><subject>Dose-Response Relationship, Drug</subject><subject>Excitatory amino acids</subject><subject>Glycine</subject><subject>Glycine - chemistry</subject><subject>Glycine - metabolism</subject><subject>hydroxy-3-amino-pyrrolid-2-one</subject><subject>Kynurenic Acid - analogs & derivatives</subject><subject>Kynurenic Acid - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>N-Methyl-D-aspartate (NMDA)</subject><subject>Neuropharmacology</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyamines</subject><subject>Pyrrolidinones - chemistry</subject><subject>Pyrrolidinones - pharmacology</subject><subject>Quinoxalines - pharmacology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Receptors, N-Methyl-D-Aspartate - drug effects</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Spermine</subject><subject>Spermine - pharmacology</subject><subject>Stereoisomerism</subject><subject>Synaptosomes - drug effects</subject><subject>Synaptosomes - metabolism</subject><issn>0922-4106</issn><issn>0014-2999</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMGK1EAQhvugrOvqGyjMQWTn0FrV6XTSF2FY1BUGBNGDp6bSqTitSXrszizO25sxw3rTU8Ff318UnxDPEF4hoHkNVimpEcy1xbUF0JXcPhCX9_Ej8Tjn7wBg0eoLcYF1oXVVXIqvm29xDHmSffjBK7-jRH7itIrdatrx6vrTWvJI4xTisKQod8c2xV9HWUgawhjl_phS7EMrlYzjXLndSGvM-ol42FGf-el5Xokv795-vrmV24_vP9xsttJrrCZZUWU8I-naQ0O1LlWruCPFrFRd26LkBnzVWKJOQT2zilvAsjTUGMMMxZV4udzdp_jzwHlyQ8ie-55GjofsKqW1Mqj_C6JBLGuoZlAvoE8x58Sd26cwUDo6BHfS7U5e3cmrs-j-6Hbbufb8fP_QDNz-LS2u5_2L856yp75LNPqQ7zFt6xK0nbE3C8aztLvAyWUfePTchsR-cm0M__7jN21wmyM</recordid><startdate>19910912</startdate><enddate>19910912</enddate><creator>Pullan, Linda M.</creator><creator>Verticelli, Adeline M.</creator><creator>Paschetto, Katherine A.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><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><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19910912</creationdate><title>Agonist-like character of the (R)-enantiomer of 1-hydroxy-3-amino-pyrrolid-2-one (HA-966)</title><author>Pullan, Linda M. ; Verticelli, Adeline M. ; Paschetto, Katherine A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-7a76ce1a48c0ba8452d2efa2ee2288935eb0c7b9aaf20876c2ed01556ab66ee03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>1-Hydroxy-3-amino-pyrrolid-2-one (HA-966)</topic><topic>Amino Acids - pharmacology</topic><topic>Amino Acids, Cyclic</topic><topic>Animals</topic><topic>Binding, Competitive</topic><topic>Biological and medical sciences</topic><topic>brain</topic><topic>Dose-Response Relationship, Drug</topic><topic>Excitatory amino acids</topic><topic>Glycine</topic><topic>Glycine - chemistry</topic><topic>Glycine - metabolism</topic><topic>hydroxy-3-amino-pyrrolid-2-one</topic><topic>Kynurenic Acid - analogs & derivatives</topic><topic>Kynurenic Acid - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>N-Methyl-D-aspartate (NMDA)</topic><topic>Neuropharmacology</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyamines</topic><topic>Pyrrolidinones - chemistry</topic><topic>Pyrrolidinones - pharmacology</topic><topic>Quinoxalines - pharmacology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Receptors, N-Methyl-D-Aspartate - drug effects</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Spermine</topic><topic>Spermine - pharmacology</topic><topic>Stereoisomerism</topic><topic>Synaptosomes - drug effects</topic><topic>Synaptosomes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pullan, Linda M.</creatorcontrib><creatorcontrib>Verticelli, Adeline M.</creatorcontrib><creatorcontrib>Paschetto, Katherine A.</creatorcontrib><collection>Pascal-Francis</collection><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><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pullan, Linda M.</au><au>Verticelli, Adeline M.</au><au>Paschetto, Katherine A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Agonist-like character of the (R)-enantiomer of 1-hydroxy-3-amino-pyrrolid-2-one (HA-966)</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1991-09-12</date><risdate>1991</risdate><volume>208</volume><issue>1</issue><spage>25</spage><epage>29</epage><pages>25-29</pages><issn>0922-4106</issn><issn>0014-2999</issn><abstract>HA-966 (1-hydroxy-3-amino-pyrrolid-2-one), an antagonist at the strychine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex, only partially inhibits the binding of noncompetitive antagonists to the NMDA receptor but enhances the binding of the NMDA competitive antagonist CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid). Here we report that the IC
50 of the active (R)-enantiomer of HA-966 for displacement of [
3H]glycine binding is decreased in the presence of spermine, suggesting that spermine increases the affinity of (R)-HA-966 at the [
3H]glycine site. The IC
50 values of the agonist glycine and the partial agonist 1-aminocyclopropane-1-carboxyalate are also decreases. The IC
50 values of glycine antagonists, 6,7-dinitroquinoxalin-2,3-dione and 7-chlorokynurenic acid are not significantly altered. The spermine shift represents the first demonstration of the agonist-like character of the (R)-enantiomer of HA-966 at the glycine site.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>1834473</pmid><doi>10.1016/0922-4106(91)90047-L</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0922-4106 |
| ispartof | European journal of pharmacology, 1991-09, Vol.208 (1), p.25-29 |
| issn | 0922-4106 0014-2999 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72442614 |
| source | MEDLINE; Elsevier ScienceDirect Journals; Alma/SFX Local Collection |
| subjects | 1-Hydroxy-3-amino-pyrrolid-2-one (HA-966) Amino Acids - pharmacology Amino Acids, Cyclic Animals Binding, Competitive Biological and medical sciences brain Dose-Response Relationship, Drug Excitatory amino acids Glycine Glycine - chemistry Glycine - metabolism hydroxy-3-amino-pyrrolid-2-one Kynurenic Acid - analogs & derivatives Kynurenic Acid - pharmacology Male Medical sciences Miscellaneous N-Methyl-D-aspartate (NMDA) Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Polyamines Pyrrolidinones - chemistry Pyrrolidinones - pharmacology Quinoxalines - pharmacology Rats Rats, Inbred Strains Receptors, N-Methyl-D-Aspartate - drug effects Receptors, N-Methyl-D-Aspartate - metabolism Spermine Spermine - pharmacology Stereoisomerism Synaptosomes - drug effects Synaptosomes - metabolism |
| title | Agonist-like character of the (R)-enantiomer of 1-hydroxy-3-amino-pyrrolid-2-one (HA-966) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T12%3A21%3A04IST&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=Agonist-like%20character%20of%20the%20(R)-enantiomer%20of%201-hydroxy-3-amino-pyrrolid-2-one%20(HA-966)&rft.jtitle=European%20journal%20of%20pharmacology&rft.au=Pullan,%20Linda%20M.&rft.date=1991-09-12&rft.volume=208&rft.issue=1&rft.spage=25&rft.epage=29&rft.pages=25-29&rft.issn=0922-4106&rft_id=info:doi/10.1016/0922-4106(91)90047-L&rft_dat=%3Cproquest_cross%3E16115807%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=16115807&rft_id=info:pmid/1834473&rft_els_id=092241069190047L&rfr_iscdi=true |