RESUMO
The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.
Assuntos
Antiarrítmicos/farmacologia , Benzamidas/farmacologia , Animais , Antiarrítmicos/efeitos adversos , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/fisiopatologia , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Cães , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Eletrocardiografia/efeitos dos fármacos , Eletrofisiologia , Humanos , RatosRESUMO
The beta- and alpha-adrenoceptor blocking activity, the specificity of its beta-adrenoceptor blocking action, partial agonistic and membrane-stabilizing properties, as well as antihypertensive, antiarrhythmic, and anti-ischemic effects were studied. Proxodolol was shown to be superior to labetalol in its beta-adrenoceptor blocking action and similar to it in its alpha-adrenoceptor blocking agent. The drug has no a partial agonistic activity and produces a moderate membrane-stabilizing action. Proxodolol proved to be effective in treating experimental hypertension and arrhythmias. It exhibits anti-ischemic activity.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Oxidiazóis/farmacologia , Antagonistas Adrenérgicos alfa/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Animais , Arritmias Cardíacas/tratamento farmacológico , Gatos , Membrana Celular/efeitos dos fármacos , Cães , Avaliação Pré-Clínica de Medicamentos , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Técnicas In Vitro , Labetalol/farmacologia , Masculino , Oxidiazóis/uso terapêutico , Oxprenolol/farmacologia , Propranolol/farmacologia , Coelhos , RatosRESUMO
Some derivatives of 2-(3-amino-2-hydroxypropoxy)phenoxymethyl isoxazole possess beta- and alpha-adrenoblocking activity. 3-Methyl-4-chlor-5-(3-isopropylamino-2-hydroxypropoxy)phenoxymethyl isoxazole hydrochloride (compound OF-4452) is the most active of the compounds studied. As to the beta-adrenoblocking activity, this compound given in vivo and in vitro compares very favourably with propranolol, oxprenolol and labetalol, in particular; as regards the alpha-adrenoblocking action, it is not inferior to the latter drug. Compound OF-4452 has a partial agonist activity and nonspecific membrane-stabilizing action. It displays antifibrillatory and antiarrhythmic activity as well.
