Linked Life Data

1819151

Source:http://linkedlifedata.com/resource/pubmed/id/1819151

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-7-20
pubmed:abstractText
The three dimensional structure, electrostatic potentials and molecular dynamics of a series of tricyclic antipsychotic drugs and metabolites were examined by computer graphics and molecular modeling techniques. Three dimensional models of the 5-HT1A and 5-HT2 receptor and of the dopamine D2 receptor were constructed from the amino acid sequences. The receptor models have strongly negative electrostatic potentials around the synaptic domains and a postulated ligand binding site. This indicates that protonated ligands are attracted to these receptors by electrostatic forces. Pharmacologically inactive trans(E)-thioxanthenes and phenothiazine ring sulphoxides had strongly negative electrostatic potentials around a part of the ring system. This may weaken their electrostatic interactions with the D2 receptor, and be the reason for their lack of potency in D2 receptor binding and related pharmacological tests. Molecular dynamics simulations in aqueous solution demonstrated that both the side chains and the tricyclic ring systems of the drugs are highly flexible, and move between different conformations in picoseconds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0040-5957
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
453-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Molecular modeling of antipsychotic drugs and G protein coupled receptors.
pubmed:affiliation
Department of Pharmacology, University of Troms, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't