Linked Life Data

6979630

Source:http://linkedlifedata.com/resource/pubmed/id/6979630

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1982-8-7
pubmed:abstractText
In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine). This led to an attempt to link every type of drug action to its own cluster of atoms. This quest was jolted when Loewi (1926) found that a quaternary amine (acetylcholine) was the principal activator of muscle! Suddenly it was seen that a chemical group could be either an agonist or antagonist, depending on its molecular setting. That the agonists were smaller molecules suggested operation of a steric factor. Moreover, Cushny (1926) had focused attention on optical enantiomers: usually only one member of each pair had biological activity, although both were identical in all other properties. The stage was now set for physical properties to play the leading role in relating structure to activity. People recalled the demonstration by Overton and Meyer (1900) that the depressant action of a drug was linked to its lipophilicity. Unhappily, further physical correlations were slow to appear. My colleagues and I, who had been studying (from 1941) the antimicrobial action of aminoacridines and hydroxyquinolines, established quantitatively the role of ionization and chelation (two electronic influences) in the action of drugs. Today most people would agree that the most important properties in determining the action of drugs are not some particular nucleus or substituent but a trio of physical properties: lipophilicity, electron distribution, and shape. Although these properties govern the activity of drugs, their selectivity is due, as I have long maintained, to another trio of properties, namely, comparative distribution (not necessarily lipophilic), comparative biochemistry, and comparative cytology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-5
pubmed:dateRevised
2000-12-18
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Fourth Smissman Award Address. The long search for valid structure-action relationships in drugs.
pubmed:publicationType
Journal Article