Linked Life Data

2837873

Source:http://linkedlifedata.com/resource/pubmed/id/2837873

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1988-7-19
pubmed:abstractText
1. Chlorpromazine (CPZ) is a unique molecule which has many potential sites of action, as well as a propensity to be transformed into a host of metabolites possessing varying degrees of pharmacological and/or toxic reactions. This investigation examined the rank order of potency of CPZ and eight metabolic derivatives with respect to displacement of 3H-spiperone at central dopamine-2 (DA-2) receptors, 3H-pirenzepine at central muscarinic-1 (M-1) receptors, and inhibition of calmodulin-induced activation of cyclic AMP-dependent phosphodiesterase. 2. The most potent CPZ analogues to displace labelled spiperone from DA-2 receptors in rat striatum were: 3-hydroxy-CPZ, CPZ, 3,7-dihydroxy-CPZ, and 7-hydroxy-CPZ. Intermediate potency was observed with 8-hydroxy-CPZ, 3,7,8-trihydroxy-CPZ, and 7,8-dihydroxy-CPZ. Chlorpromazine sulphoxide and 7,8-dimethoxy-CPZ displayed the least activity at DA-2 receptors. 3. Displacement of labelled pirenzepine from M-1 receptors in rat frontal cortex occurred to the greatest extent with CPZ which was one to two orders of magnitude more potent than noted for 3-hydroxy-CPZ greater than 7-hydroxy-CPZ greater than CPZ-sulphoxide greater than 8-hydroxy-CPZ greater than 7,8-dimethoxy-CPZ. The least potent agents were 3,7-and 7,8-dihydroxy-CPZs and 3,7,8-trihydroxy-CPZ. 4. A partially purified calmodulin-sensitive preparation of cyclic AMP-dependent phosphodiesterase from guinea pig heart was most sensitive to inhibition by 7,8-dihydroxy-CPZ, 7,8-dimethoxy-CPZ, 3-hydroxy-CPZ, 7-hydroxy-CPZ, 8-hydroxy-CPZ and CPZ. Least inhibition occurred with 3,7-dihydroxy-CPZ, 3,7,8-trihydroxy-CPZ and CPZ-sulphoxide. 5. The DA-2 receptors were more sensitive to the active CPZ analogues than were the M-1 receptors while calmodulin-activated phosphodiesterase was the least sensitive preparation. 6. Comparisons of data were made with existing information from other laboratories and in general CPZ, 7-hydroxy-CPZ and 3-hydroxy-CPZ were the most potent compounds across different test conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
277-89
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Correlation of activity of chlorpromazine and respective hydroxy, dimethoxy and sulphoxide analogues on dopamine, muscarinic, histamine and calmodulin sites of action.
pubmed:affiliation
Pharmacology Department, Pennwalt Corporation, Rochester, NY 14623.
pubmed:publicationType
Journal Article