Linked Life Data

6112947

Source:http://linkedlifedata.com/resource/pubmed/id/6112947

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1981-7-9
pubmed:abstractText
A number of psychotropic drugs, particularly the phenothiazines and related antipsychotic compounds, inhibit a variety of calmodulin-dependent enzymes. The mechanism by which these compounds inhibit the activity of calmodulin is through a selective calcium-dependent binding to this protein. With the notable exception of certain stereoisomers, compounds that are clinically effective antipsychotic agents showed the greatest degree of binding to calmodulin. Other classes of pharmacological agents, including aminergic agonists and antagonists, and nonspecific central nervous system depressants and stimulants, showed little or no binding to calmodulin. In fact, the specificity with which antipsychotic drugs bind to calmodulin suggests the possibility of screening for new and clinically more effective antipsychotic agents based on their selective binding to calmodulin. Certain neuropeptides that produce behavioral effects in animals also were found to inhibit the activity of calmodulin, suggesting that there may be endogenous psychotogens or antipsychotic peptides that interact with calmodulin. Although under ordinary conditions the binding of antipsychotics to calmodulin is reversible, the binding of phenothiazine antipsychotics to calmodulin can be made irreversible either photochemically by ultraviolet irradiation, or enzymatically by a hydrogen peroxide-peroxidase system. Such a labeling technique should prove to be a useful tool to study the localization and turnover of calmodulin. These results indicate that several of the diverse biochemical actions of antipsychotic agents can be explained by a common mechanism, namely, by their binding to and inhibition of calmodulin, and raise the possibility that calmodulin may serve as one of the cellular receptors for certain antipsychotic compounds. However, further studies must be completed before we can state with any degree of certainty that these in vitro biochemical findings can explain the pharmacological and clinical actions of the antipsychotics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3',5'-Cyclic-AMP Phosphodiesterases, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase, http://linkedlifedata.com/resource/pubmed/chemical/Antipsychotic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide..., http://linkedlifedata.com/resource/pubmed/chemical/Endorphins, http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase, http://linkedlifedata.com/resource/pubmed/chemical/Hormones, http://linkedlifedata.com/resource/pubmed/chemical/Phenothiazines, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases
pubmed:status
MEDLINE
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
356
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
319-45
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1980
pubmed:articleTitle
Pharmacological regulation of calmodulin.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review