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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1997-8-27
|
| pubmed:abstractText |
The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(l-(alpha-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4-tetrah ydroquinoline -6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca(2+)-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca(2+)-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 microM) shifted the EC50 of Ca2+ for contractile activation of skinned fibers of pig heart from 2.41 microM to 0.73 microM, whereas [-]-EMD 60264 (30 microM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35% of pre-drug control with [+]-EMD 60263 in comparison to 113% with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component IKr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define IKr.
|
| 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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/EMD 60263,
http://linkedlifedata.com/resource/pubmed/chemical/Thiadiazines
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0028-1298
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
355
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
733-42
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9205958-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:9205958-Action Potentials,
pubmed-meshheading:9205958-Animals,
pubmed-meshheading:9205958-Atrial Function,
pubmed-meshheading:9205958-Calcium,
pubmed-meshheading:9205958-Cyclic Nucleotide Phosphodiesterases, Type 3,
pubmed-meshheading:9205958-Electric Stimulation,
pubmed-meshheading:9205958-Guinea Pigs,
pubmed-meshheading:9205958-Heart Rate,
pubmed-meshheading:9205958-Heart Ventricles,
pubmed-meshheading:9205958-Humans,
pubmed-meshheading:9205958-Male,
pubmed-meshheading:9205958-Membrane Potentials,
pubmed-meshheading:9205958-Myocardial Contraction,
pubmed-meshheading:9205958-Papillary Muscles,
pubmed-meshheading:9205958-Patch-Clamp Techniques,
pubmed-meshheading:9205958-Stereoisomerism,
pubmed-meshheading:9205958-Swine,
pubmed-meshheading:9205958-Thiadiazines,
pubmed-meshheading:9205958-Ventricular Function
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264.
|
| pubmed:affiliation |
Institut für Pharmakologie, Universitätsklinikum Essen, Germany.
|
| pubmed:publicationType |
Journal Article,
In Vitro
|