| pubmed-article:17157509 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17157509 | lifeskim:mentions | umls-concept:C0080093 | lld:lifeskim |
| pubmed-article:17157509 | lifeskim:mentions | umls-concept:C0038477 | lld:lifeskim |
| pubmed-article:17157509 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:17157509 | pubmed:dateCreated | 2007-1-8 | lld:pubmed |
| pubmed-article:17157509 | pubmed:abstractText | Prompted by our interest in neuroprotective agents with multiple mechanisms of action, we assessed the structure-activity relationship of a series of pentacycloundecylamine derivatives previously shown to have both L-type calcium channel blocking activity and N-methyl-d-aspartate receptor (NMDAR) antagonistic activity. We utilized a functional assay to measure NMDAR channel block using (45)Ca(2+) influx into synaptoneurosomes. The cage amine 8-benzylamino-8,11-oxapentacyclo[5.4.0.0(2,6). 0(3,10).0(5,9)]undecane (NPG1-01) proved to be the most potent experimental compound with an IC(50) of 2.98microM, while 8-amino-pentacyclo[5.4.0.0(2,6).0(3,10).0(5,9)]undecane had the next most potent IC(50) of 4.06microM. Increasing the polycyclic cage size of NGP1-01 from a pentacycloundecane to a tridecane cage structure, but retaining the N-benzyl moiety decreased potency 10-fold, indicating a limitation on the volume of the cage that can be accommodated in the channel binding site. In the presence of NGP1-01, NMDA/glycine-induced maximal (45)Ca(2+) influx was attenuated by 34% with an insignificant effect on agonist potency. These results are consistent with uncompetitive antagonism for this group of compounds. Radioligand binding studies with [(3)H]MK-801 or [(3)H]TCP showed little or no displacement of these ligands by pentacycloundecylamines, suggesting that the latter compounds bind to a unique site in the NMDAR channel. The pentacycloundecylamines tested represent a novel group of NMDAR antagonists that have potential as therapeutic agents for neurodegenerative diseases including Parkinson's and Alzheimer's disease. | lld:pubmed |
| pubmed-article:17157509 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17157509 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17157509 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17157509 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:17157509 | pubmed:issn | 0968-0896 | lld:pubmed |
| pubmed-article:17157509 | pubmed:author | pubmed-author:BloomquistJef... | lld:pubmed |
| pubmed-article:17157509 | pubmed:author | pubmed-author:MalanSarel... | lld:pubmed |
| pubmed-article:17157509 | pubmed:author | pubmed-author:Van der... | lld:pubmed |
| pubmed-article:17157509 | pubmed:author | pubmed-author:GeldenhuysWer... | lld:pubmed |
| pubmed-article:17157509 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17157509 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:17157509 | pubmed:volume | 15 | lld:pubmed |
| pubmed-article:17157509 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17157509 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17157509 | pubmed:pagination | 1525-32 | lld:pubmed |
| pubmed-article:17157509 | pubmed:meshHeading | pubmed-meshheading:17157509... | lld:pubmed |
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| pubmed-article:17157509 | pubmed:meshHeading | pubmed-meshheading:17157509... | lld:pubmed |
| pubmed-article:17157509 | pubmed:meshHeading | pubmed-meshheading:17157509... | lld:pubmed |
| pubmed-article:17157509 | pubmed:meshHeading | pubmed-meshheading:17157509... | lld:pubmed |
| pubmed-article:17157509 | pubmed:meshHeading | pubmed-meshheading:17157509... | lld:pubmed |
| pubmed-article:17157509 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17157509 | pubmed:articleTitle | Structure-activity relationships of pentacycloundecylamines at the N-methyl-d-aspartate receptor. | lld:pubmed |
| pubmed-article:17157509 | pubmed:affiliation | Department of Pharmaceutical Sciences, Northeastern Ohio Universities College of Pharmacy, Rootstown, OH 44272-0095, USA. | lld:pubmed |
| pubmed-article:17157509 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17157509 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | http://linkedlifedata.com/r... | pubmed-article:17157509 | lld:chembl |
