Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy: Theoretical, Experimental, and Clinical Study
Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the “guarded-receptor” model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excita...
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| Veröffentlicht in: | Journal of cardiovascular pharmacology 1994-03, Vol.23 (3), p.501-508 |
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| container_title | Journal of cardiovascular pharmacology |
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| creator | Nesterenko, Vladislav V Anyukhovsky, Evgeny P Bugrij, Evgeny M Starmer, Frank C Beloshapko, Galina G Makielski, Jonathan C Kuzmin, Alexander V Menshikov, Mikhail Ju Mazaev, Alexey V Rosenshtraukh, Leonid V |
| description | Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the “guarded-receptor” model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals |
| doi_str_mv | 10.1097/00005344-199403000-00021 |
| format | Article |
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Computer simulation using the “guarded-receptor” model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals <600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 ± 13% for 400 and 800 mg/day ethmozin and 18 ± 12 and 55 ± 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 ± 2% in these patients without side effects. In the “nonresistant” but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with “fast-off” and one with “slow-off” kinetics, which may provide a general rationale for choosing drug combinations.</description><identifier>ISSN: 0160-2446</identifier><identifier>EISSN: 1533-4023</identifier><identifier>DOI: 10.1097/00005344-199403000-00021</identifier><identifier>PMID: 7515997</identifier><identifier>CODEN: JCPCDT</identifier><language>eng</language><publisher>Philadelphia, PA: Lippincott-Raven Publishers</publisher><subject>Adult ; Animals ; Anti-Arrhythmia Agents - adverse effects ; Anti-Arrhythmia Agents - therapeutic use ; Arrhythmias, Cardiac - drug therapy ; Arrhythmias, Cardiac - physiopathology ; Computer Simulation ; Dogs ; Drug Therapy, Combination ; Electric Stimulation ; Electrocardiography ; Female ; Heart Conduction System - drug effects ; Heart Rate - drug effects ; Heart Ventricles - physiopathology ; Humans ; Male ; Middle Aged ; Models, Biological ; Moricizine - adverse effects ; Moricizine - analogs & derivatives ; Moricizine - therapeutic use ; Receptors, Drug - drug effects ; Sodium Channels - drug effects</subject><ispartof>Journal of cardiovascular pharmacology, 1994-03, Vol.23 (3), p.501-508</ispartof><rights>Lippincott-Raven Publishers.</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf><![CDATA[$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&PDF=y&D=ovft&AN=00005344-199403000-00021$$EPDF$$P50$$Gwolterskluwer$$H]]></linktopdf><linktohtml>$$Uhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00005344-199403000-00021$$EHTML$$P50$$Gwolterskluwer$$H</linktohtml><link.rule.ids>314,780,784,4609,27924,27925,64666,65461</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3960748$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7515997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nesterenko, Vladislav V</creatorcontrib><creatorcontrib>Anyukhovsky, Evgeny P</creatorcontrib><creatorcontrib>Bugrij, Evgeny M</creatorcontrib><creatorcontrib>Starmer, Frank C</creatorcontrib><creatorcontrib>Beloshapko, Galina G</creatorcontrib><creatorcontrib>Makielski, Jonathan C</creatorcontrib><creatorcontrib>Kuzmin, Alexander V</creatorcontrib><creatorcontrib>Menshikov, Mikhail Ju</creatorcontrib><creatorcontrib>Mazaev, Alexey V</creatorcontrib><creatorcontrib>Rosenshtraukh, Leonid V</creatorcontrib><title>Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy: Theoretical, Experimental, and Clinical Study</title><title>Journal of cardiovascular pharmacology</title><addtitle>J Cardiovasc Pharmacol</addtitle><description>Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the “guarded-receptor” model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals <600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 ± 13% for 400 and 800 mg/day ethmozin and 18 ± 12 and 55 ± 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 ± 2% in these patients without side effects. In the “nonresistant” but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with “fast-off” and one with “slow-off” kinetics, which may provide a general rationale for choosing drug combinations.</description><subject>Adult</subject><subject>Animals</subject><subject>Anti-Arrhythmia Agents - adverse effects</subject><subject>Anti-Arrhythmia Agents - therapeutic use</subject><subject>Arrhythmias, Cardiac - drug therapy</subject><subject>Arrhythmias, Cardiac - physiopathology</subject><subject>Computer Simulation</subject><subject>Dogs</subject><subject>Drug Therapy, Combination</subject><subject>Electric Stimulation</subject><subject>Electrocardiography</subject><subject>Female</subject><subject>Heart Conduction System - drug effects</subject><subject>Heart Rate - drug effects</subject><subject>Heart Ventricles - physiopathology</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Moricizine - adverse effects</subject><subject>Moricizine - analogs & derivatives</subject><subject>Moricizine - therapeutic use</subject><subject>Receptors, Drug - drug effects</subject><subject>Sodium Channels - drug effects</subject><issn>0160-2446</issn><issn>1533-4023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1UU1rGzEQFSUlcZP-hIIOPWbbmdXHWrkV435AoNC6uS5jrYSVrHeNJJO6_fPV1q5vFQjx5r03zDwxxhHeIZjmPZSjhJQVGiNBFFSVW-MLNkMlRCWhFhdsBqihqqXUV-xVSo8AKFWjL9llo1AZ08zY78W4XYeBchgHvswbsuFXGDgN3YS24wRW0VHeuiHz0fNvLoWUqYCHUonB7nuKfGnzuDvc8dXGjdHlYKm_5cufOxfDZJzQ1HLRh2Hi-Pe87w437KWnPrnXp_ea_fi4XC0-V_dfP31ZfLivbBkdKwKce18LqTotZdd5YRyuawTlCDsPBtGC0V6A1o0GDWipVqruSJAjo8U1mx_72jimFJ1vd2UsiocWoZ3ibP_F2Z7jbP_GWaxvjtbdfr113dl4yq_wb088pbKXjzTYkM4yYTQ0cl5k8ih7HvvsYnrq988uthtHfd60__tM8QfRa42I</recordid><startdate>199403</startdate><enddate>199403</enddate><creator>Nesterenko, Vladislav V</creator><creator>Anyukhovsky, Evgeny P</creator><creator>Bugrij, Evgeny M</creator><creator>Starmer, Frank C</creator><creator>Beloshapko, Galina G</creator><creator>Makielski, Jonathan C</creator><creator>Kuzmin, Alexander V</creator><creator>Menshikov, Mikhail Ju</creator><creator>Mazaev, Alexey V</creator><creator>Rosenshtraukh, Leonid V</creator><general>Lippincott-Raven Publishers</general><general>Lippincott</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>199403</creationdate><title>Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy: Theoretical, Experimental, and Clinical Study</title><author>Nesterenko, Vladislav V ; Anyukhovsky, Evgeny P ; Bugrij, Evgeny M ; Starmer, Frank C ; Beloshapko, Galina G ; Makielski, Jonathan C ; Kuzmin, Alexander V ; Menshikov, Mikhail Ju ; Mazaev, Alexey V ; Rosenshtraukh, Leonid V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2441-a018ff2345d644ddf39e1b2105ea1df0911c096f3066760601ca2552da3aea963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Anti-Arrhythmia Agents - adverse effects</topic><topic>Anti-Arrhythmia Agents - therapeutic use</topic><topic>Arrhythmias, Cardiac - drug therapy</topic><topic>Arrhythmias, Cardiac - physiopathology</topic><topic>Computer Simulation</topic><topic>Dogs</topic><topic>Drug Therapy, Combination</topic><topic>Electric Stimulation</topic><topic>Electrocardiography</topic><topic>Female</topic><topic>Heart Conduction System - drug effects</topic><topic>Heart Rate - drug effects</topic><topic>Heart Ventricles - physiopathology</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>Moricizine - adverse effects</topic><topic>Moricizine - analogs & derivatives</topic><topic>Moricizine - therapeutic use</topic><topic>Receptors, Drug - drug effects</topic><topic>Sodium Channels - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nesterenko, Vladislav V</creatorcontrib><creatorcontrib>Anyukhovsky, Evgeny P</creatorcontrib><creatorcontrib>Bugrij, Evgeny M</creatorcontrib><creatorcontrib>Starmer, Frank C</creatorcontrib><creatorcontrib>Beloshapko, Galina G</creatorcontrib><creatorcontrib>Makielski, Jonathan C</creatorcontrib><creatorcontrib>Kuzmin, Alexander V</creatorcontrib><creatorcontrib>Menshikov, Mikhail Ju</creatorcontrib><creatorcontrib>Mazaev, Alexey V</creatorcontrib><creatorcontrib>Rosenshtraukh, Leonid V</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of cardiovascular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nesterenko, Vladislav V</au><au>Anyukhovsky, Evgeny P</au><au>Bugrij, Evgeny M</au><au>Starmer, Frank C</au><au>Beloshapko, Galina G</au><au>Makielski, Jonathan C</au><au>Kuzmin, Alexander V</au><au>Menshikov, Mikhail Ju</au><au>Mazaev, Alexey V</au><au>Rosenshtraukh, Leonid V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy: Theoretical, Experimental, and Clinical Study</atitle><jtitle>Journal of cardiovascular pharmacology</jtitle><addtitle>J Cardiovasc Pharmacol</addtitle><date>1994-03</date><risdate>1994</risdate><volume>23</volume><issue>3</issue><spage>501</spage><epage>508</epage><pages>501-508</pages><issn>0160-2446</issn><eissn>1533-4023</eissn><coden>JCPCDT</coden><abstract>Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the “guarded-receptor” model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals <600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 ± 13% for 400 and 800 mg/day ethmozin and 18 ± 12 and 55 ± 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 ± 2% in these patients without side effects. In the “nonresistant” but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with “fast-off” and one with “slow-off” kinetics, which may provide a general rationale for choosing drug combinations.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>Lippincott-Raven Publishers</pub><pmid>7515997</pmid><doi>10.1097/00005344-199403000-00021</doi><tpages>8</tpages></addata></record> |
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| ispartof | Journal of cardiovascular pharmacology, 1994-03, Vol.23 (3), p.501-508 |
| issn | 0160-2446 1533-4023 |
| language | eng |
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| source | MEDLINE; Journals@Ovid LWW Legacy Archive; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Animals Anti-Arrhythmia Agents - adverse effects Anti-Arrhythmia Agents - therapeutic use Arrhythmias, Cardiac - drug therapy Arrhythmias, Cardiac - physiopathology Computer Simulation Dogs Drug Therapy, Combination Electric Stimulation Electrocardiography Female Heart Conduction System - drug effects Heart Rate - drug effects Heart Ventricles - physiopathology Humans Male Middle Aged Models, Biological Moricizine - adverse effects Moricizine - analogs & derivatives Moricizine - therapeutic use Receptors, Drug - drug effects Sodium Channels - drug effects |
| title | Combination Ethacizin and Ethmozin Treatment of Resistant Ventricular Ectopy: Theoretical, Experimental, and Clinical Study |
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