Investigation on SCH00013, a Novel Cardiotonic Agent with Ca++ Sensitizing Action
| Autor: | Mitsuo Sakato, Akira Yoshimura, Masataka Hino, Masao Endoh, Hiromi Sugawara, Kimitomo Yoshioka |
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| Rok vydání: | 2011 |
| Předmět: |
Chronotropic
medicine.medical_specialty Heart disease Refractory period Hemodynamics chemistry.chemical_compound In vivo Internal medicine Heart rate Drug Discovery medicine Vesnarinone biology business.industry Chemistry Fissipedia Effective refractory period Phosphodiesterase Biological activity biology.organism_classification medicine.disease Epinephrine Blood pressure Endocrinology Mechanism of action Enzyme inhibitor Ventricular fibrillation Cardiology biology.protein medicine.symptom business medicine.drug |
| Zdroj: | Arzneimittelforschung. 49:412-419 |
| ISSN: | 1616-7066 0004-4172 |
| Popis: | Influence of 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]- 1,2,5,6,-tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013) and vesnarinone (CAS 81840-15-5) on the arrhythmia experimentally induced by three different methods was investigated in dogs. In digitalis-induced arrhythmia, SCH00013 (3 mg/kg i.v.) showed a tendency to improve the arrhythmia with a decrease in the arrhythmic ratio and an increase in the conducted beats (CB), though these changes did not reach a significant level; it decreased significantly the blood pressure (BP) with no change in the total heart rate (THR) and atrial rate (AR). Vesnarinone (3 mg/kg i.v.) did not affect these parameters except for BP that was decreased significantly. In two-stage coronary ligation-induced arrhythmia, SCH00013 (1 and 3 mg/kg i.v.) did not change the arrhythmic ratio, CB, AR and BP, while the THR being slightly decreased; the arrhythmic ratio showed a tendency to decrease with SCH00013 when examined at 24 h after coronary ligation. Vesnarinone (3 mg/kg i.v.) did not affect these parameters at 24 and 48 h after ligation. In epinephrine (adrenaline)-induced arrhythmia, both SCH00013 and vesnarinone showed exacerbation of arrhythmia. SCH00013 at 1 mg/kg i.v. did not elicit ventricular fibrillation (VF) in five dogs examined, but at 3 mg/kg i.v. it elicited VF in two of three dogs. Vesnarinone at 1 mg/kg i.v. induced VF in all of three dogs examined. Incidence of VF induced by optical isomers of SCH00013 was not significantly different from each other: both isomers elicited VF in two of six dogs at 1 mg/kg i.v. and at 3 mg/kg i.v. each of them induced VF in two dogs examined. The present results indicate that SCH00013 is a cardiotonic agent that is equivalent to or less arrhythmogenic than vesnarinone in animal models of arrhythmia, such as adrenaline- and digitalis-induced arrhythmia and the two-stage coronary ligation-induced arrhythmia. Optical isomers of SCH00013 were essentially equieffective in eliciting exacerbation of adrenaline-induced arrhythmia in the dog. |
| Databáze: | OpenAIRE |
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