Linked Life Data

3063437

Source:http://linkedlifedata.com/resource/pubmed/id/3063437

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-3-9
pubmed:abstractText
The calcium antagonists prenylamine and fendiline both bind with rather low affinity to the dihydropyridine (nifedipine) binding site. As calmodulin (CaM) antagonists, they both inhibit CaM-dependent enzymes and relax smooth muscle preparation in nearly the same concentration range. If compared with other calcium antagonists, their action on smooth muscle develops rather slowly and cannot be inhibited by the calcium agonist Bay k 8644. In contrast, basic pharmacology reveals major differences of the actions of prenylamine and fendiline in heart muscle, indicating that, after all, the change in structure close to the asymmetric carbon strongly influences the molecular action of the compounds and their respective isomers. The negative inotropic effect of racemic prenylamine is rather independent of stimulation rate, whereas fendiline preferably depresses contraction at high rate stimulation. The negative inotropic potencies are determined by the (-)-isomers, but only in the case of prenylamine the isomeric ratio of 6 reveals a considerable stereoselectivity of action. In low concentrations and preferably at low rate stimulation, (+)-prenylamine exerts a strong positive inotropic effect. At low rate stimulation, total duration of transmembrane action potential is prolonged by (+/-)- and (+)-prenylamine, but discretely shortened by (+/-)- and (+)-fendiline. At high rate stimulation, it is shortened by (+/-)- and (-)-prenylamine, but prolonged (only) at the very final repolarization level by (+/-)- and (-)-fendiline. The positive inotropic action of prenylamine and the prolongation of action potential at low stimulation rate can be interpreted as a calcium agonistic side-effect due to the action of the (+)-isomer. It seems possible that, under the condition of low heart rate, prenylamine (as reported for the calcium agonist Bay k 8644) increases the potential-dependent transmembrane calcium current. In addition, it is argued that during the long-lasting action potential, a reactivation of the calcium current induces early after-depolarizations. These effects are postulated to represent the main mechanisms triggering torsade de pointes during therapy with prenylamine. Though fendiline, from a chemical point of view, rather resembles prenylamine, its pharmacological profile is different. In particular, in regard to electrophysiology, torsade de pointes are not expected to be induced by fendiline.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0300-7995
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
254-72
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Basic mechanisms underlying prenylamine-induced 'torsade de pointes': differences between prenylamine and fendiline due to basic actions of the isomers.
pubmed:affiliation
Institute for Clinical Physiology, University of Düsseldorf, Federal Republic of Germany.
pubmed:publicationType
Journal Article, Comparative Study, Review