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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-4-1
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pubmed:abstractText |
Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the alpha(2)-delta subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their alpha(2)-delta binding affinity as demonstrated by their ability to inhibit binding of [(3)H]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [(3)H]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for alpha(2)-delta binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amines,
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Transport System L,
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Anxiety Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Anticonvulsants,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclohexanecarboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/gabapentin,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid,
http://linkedlifedata.com/resource/pubmed/chemical/pregabalin
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BelliottiThomas RTR,
pubmed-author:CapirisThomasT,
pubmed-author:EkhatoI VictorIV,
pubmed-author:FieldMark JMJ,
pubmed-author:HeffnerThomas GTG,
pubmed-author:KinsoraJack JJJ,
pubmed-author:MeltzerLeonard TLT,
pubmed-author:SchwarzJacob BJB,
pubmed-author:TaylorCharles PCP,
pubmed-author:ThorpeAndrew JAJ,
pubmed-author:VartanianMark GMG,
pubmed-author:WeberMark LML,
pubmed-author:WiseLawrence DLD,
pubmed-author:WustrowDavid JDJ,
pubmed-author:Zhi-SuTiT
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2294-307
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15801823-Amines,
pubmed-meshheading:15801823-Amino Acid Transport System L,
pubmed-meshheading:15801823-Analgesics,
pubmed-meshheading:15801823-Animals,
pubmed-meshheading:15801823-Anti-Anxiety Agents,
pubmed-meshheading:15801823-Anticonvulsants,
pubmed-meshheading:15801823-Brain,
pubmed-meshheading:15801823-CHO Cells,
pubmed-meshheading:15801823-Calcium Channels,
pubmed-meshheading:15801823-Cricetinae,
pubmed-meshheading:15801823-Cricetulus,
pubmed-meshheading:15801823-Cyclohexanecarboxylic Acids,
pubmed-meshheading:15801823-Leucine,
pubmed-meshheading:15801823-Male,
pubmed-meshheading:15801823-Mice,
pubmed-meshheading:15801823-Mice, Inbred DBA,
pubmed-meshheading:15801823-Protein Binding,
pubmed-meshheading:15801823-Protein Subunits,
pubmed-meshheading:15801823-Rats,
pubmed-meshheading:15801823-Structure-Activity Relationship,
pubmed-meshheading:15801823-Swine,
pubmed-meshheading:15801823-gamma-Aminobutyric Acid
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pubmed:year |
2005
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pubmed:articleTitle |
Structure-activity relationships of pregabalin and analogues that target the alpha(2)-delta protein.
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pubmed:affiliation |
Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor Campus, Ann Arbor, MI, 48105, USA.
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pubmed:publicationType |
Journal Article,
In Vitro
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