Computer aided development of antiarrhythmic agents with class iiia properties.
Most antiarrhythmic agents were discovered accidentally. In the last decade, the understanding of the mechanisms of action of agents with electrophysiologic activity has progressed greatly. As a result, it was possible to compute, before the CAST trial, that the agents selected for the trial would n...
| Publicado en: | Journal of Cardiovascular Electrophysiology Vol. 5; no. 8; pp. 711 - 722 |
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| Autor principal: | |
| Formato: | Journal Article |
| Publicado: |
Wiley-Blackwell
Aug1994
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=106088663&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 106088663 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10453873 GSB jtl: Journal of Cardiovascular Electrophysiology issn: 10453873 maglogo: Y pubinfo: dt: Aug1994 vid: 5 iid: 8 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 106088663 2009418298 NLM7528608 106088663 ppf: 711 ppct: 11 formats: fmt: @attributes: type: P tig: atl: Computer aided development of antiarrhythmic agents with class iiia properties. aug: au: Hondeghem LM sug: subj: Antiarrhythmia Agents Pharmacodynamics Animals Computers and Computerization Membrane Proteins Drug Effects ab: Most antiarrhythmic agents were discovered accidentally. In the last decade, the understanding of the mechanisms of action of agents with electrophysiologic activity has progressed greatly. As a result, it was possible to compute, before the CAST trial, that the agents selected for the trial would not he effective against tachycardias and that the drugs would he unsafe. Extension of these computations to existing Class I agents indicated that they were all poor suppressors of ventricular tachycardia. Furthermore, a Class I agent with an optimal electrophysiologic profile still computes to he a two-edged sword, possessing both antiarrhythmic and proarrhythmic properties. Fortunately, it is possible to conceive of drug profiles that would be purer antiarrhythmic agents. For example, a drug that only upon the development of a tachycardia lengthens action potential duration in a use-dependent manner until the refractory period exceeds the tachycardia cycle length will render continuation of the tachycardia impossible. Recognition of chemicals that have Class IIIa properties with the appropriate kinetics is a challenging task. However, today's microprocessors have become powerful enough to characterize the Class III kinetics. A system that fully automatically screens for effective antiarrhythmic agents is described. It is expected that chemicals selected for optimal basic electro-physiologic properties will yield safer and more effective antiarrhythmic agents. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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