Effect of metabolites of valproic acid on the metabolism of GABA in brain and brain nerve endings
Seven metabolites of valproic acid (VPA), i.e. 2-en-VPA, 3-en-VPA, 4-en-VPA, 3-hydroxy-VPA, 4-hydroxy-VPA, 5-hydroxy-VPA and 3-keto-VPA and valproic acid itself were examined for their effects on the metabolism of γ-aminobutyric acid (GABA) in the brain and brain nerve endings (synaptosomes) in mice...
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| Veröffentlicht in: | Neuropharmacology 1981-12, Vol.20 (12), p.1187-1192 |
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| container_title | Neuropharmacology |
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| creator | Löscher, W. Böhme, G. Schäfer, H. Kochen, W. |
| description | Seven metabolites of valproic acid (VPA), i.e. 2-en-VPA, 3-en-VPA, 4-en-VPA, 3-hydroxy-VPA, 4-hydroxy-VPA, 5-hydroxy-VPA and 3-keto-VPA and valproic acid itself were examined for their effects on the metabolism of γ-aminobutyric acid (GABA) in the brain and brain nerve endings (synaptosomes) in mice. Administered in anticonvulsant doses, valproic acid and its metabolites caused elevations of the synaptosomal GABA content which were correlated with their anticonvulsant potency. No relationship was observed between the relative anticonvulsant activity of the respective compounds and the increase of GABA in the whole brain. The synaptosomal activity of glutamate decarboxylase (GAD) was increased parallel to the elevation of GABA and the activity of GABA aminotransferase (GABA-T) was partly inhibited. The present results emphasise the usefulness of determining the
in vivo effects of drugs on GABA metabolism in brain nerve terminals which is thought to be the critical factor controlling the functioning of the amino acid as a neurotransmitter. |
| doi_str_mv | 10.1016/0028-3908(81)90062-9 |
| format | Article |
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in vivo effects of drugs on GABA metabolism in brain nerve terminals which is thought to be the critical factor controlling the functioning of the amino acid as a neurotransmitter.</description><subject>4-Aminobutyrate Transaminase - metabolism</subject><subject>Animals</subject><subject>brain</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Brain - metabolism</subject><subject>GABA</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Glutamate Decarboxylase - metabolism</subject><subject>Male</subject><subject>metabolites</subject><subject>Mice</subject><subject>nerve endings</subject><subject>Nerve Endings - drug effects</subject><subject>Nerve Endings - metabolism</subject><subject>Synaptosomes - metabolism</subject><subject>valproic acid</subject><subject>Valproic Acid - metabolism</subject><subject>Valproic Acid - pharmacology</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1981</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEQgIMotT7-gcKeRA-reWw3k4tQiy8oeNFzSLITjexDk23Bf--uLT16mUyYb2aSj5AzRq8ZZeUNpRxyoShcArtSlJY8V3tkykCKXNKy2CfTHXJIjlL6pJQWwGBCJqVUUMBsSsy99-j6rPNZg72xXR16TON1beqv2AWXGReqrGuz_gN3TGpG5HF-N89Cm9lohmjaapu1GNeYYVuF9j2dkANv6oSn2_OYvD3cvy6e8uXL4_NivsydmMk-ryzznhvgUDiOChRXEqkrLcyUlExRZkshLDVc2UJCNUPvTCGAOSut8oU4JhebucOrv1eYet2E5LCuTYvdKmkpQAjOYQCLDehil1JEr79iaEz80Yzq0awetelRmwam_8xqNbSdb-evbIPVrmmrcqjfbuo4fHIdMOrkArYOqxAHw7rqwv8LfgHUKocO</recordid><startdate>198112</startdate><enddate>198112</enddate><creator>Löscher, W.</creator><creator>Böhme, G.</creator><creator>Schäfer, H.</creator><creator>Kochen, W.</creator><general>Elsevier 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>7X8</scope></search><sort><creationdate>198112</creationdate><title>Effect of metabolites of valproic acid on the metabolism of GABA in brain and brain nerve endings</title><author>Löscher, W. ; Böhme, G. ; Schäfer, H. ; Kochen, W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-db1ff2a8284c2e989297e0c6b859771901b633b0a29b478d5efca4381cb7b9f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1981</creationdate><topic>4-Aminobutyrate Transaminase - metabolism</topic><topic>Animals</topic><topic>brain</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>Brain - metabolism</topic><topic>GABA</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Glutamate Decarboxylase - metabolism</topic><topic>Male</topic><topic>metabolites</topic><topic>Mice</topic><topic>nerve endings</topic><topic>Nerve Endings - drug effects</topic><topic>Nerve Endings - metabolism</topic><topic>Synaptosomes - metabolism</topic><topic>valproic acid</topic><topic>Valproic Acid - metabolism</topic><topic>Valproic Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Löscher, W.</creatorcontrib><creatorcontrib>Böhme, G.</creatorcontrib><creatorcontrib>Schäfer, H.</creatorcontrib><creatorcontrib>Kochen, W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Löscher, W.</au><au>Böhme, G.</au><au>Schäfer, H.</au><au>Kochen, W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of metabolites of valproic acid on the metabolism of GABA in brain and brain nerve endings</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>1981-12</date><risdate>1981</risdate><volume>20</volume><issue>12</issue><spage>1187</spage><epage>1192</epage><pages>1187-1192</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><abstract>Seven metabolites of valproic acid (VPA), i.e. 2-en-VPA, 3-en-VPA, 4-en-VPA, 3-hydroxy-VPA, 4-hydroxy-VPA, 5-hydroxy-VPA and 3-keto-VPA and valproic acid itself were examined for their effects on the metabolism of γ-aminobutyric acid (GABA) in the brain and brain nerve endings (synaptosomes) in mice. Administered in anticonvulsant doses, valproic acid and its metabolites caused elevations of the synaptosomal GABA content which were correlated with their anticonvulsant potency. No relationship was observed between the relative anticonvulsant activity of the respective compounds and the increase of GABA in the whole brain. The synaptosomal activity of glutamate decarboxylase (GAD) was increased parallel to the elevation of GABA and the activity of GABA aminotransferase (GABA-T) was partly inhibited. The present results emphasise the usefulness of determining the
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| fulltext | fulltext |
| identifier | ISSN: 0028-3908 |
| ispartof | Neuropharmacology, 1981-12, Vol.20 (12), p.1187-1192 |
| issn | 0028-3908 1873-7064 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 4-Aminobutyrate Transaminase - metabolism Animals brain Brain - drug effects Brain - enzymology Brain - metabolism GABA gamma-Aminobutyric Acid - metabolism Glutamate Decarboxylase - metabolism Male metabolites Mice nerve endings Nerve Endings - drug effects Nerve Endings - metabolism Synaptosomes - metabolism valproic acid Valproic Acid - metabolism Valproic Acid - pharmacology |
| title | Effect of metabolites of valproic acid on the metabolism of GABA in brain and brain nerve endings |
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