RESUMEN
The effects of intravenous infusions of paroxetine, a novel inhibitor of 5-hydroxytryptamine (5HT) uptake, and of the tricyclic antidepressant, amitriptyline, on the cardiovascular system have been compared in the conscious rabbit and in the anaesthetised cat. As judged by the dose required to produce changes in ECG waveform (including PR and QTc intervals) and disorders of heart rhythm, paroxetine was less cardiotoxic than amitriptyline in both species. Thus, paroxetine has the advantage over amitriptyline of being less toxic to the cardiovascular system which could constitute a considerable advantage in clinical use particularly as other work has shown it to be more potent than amitriptyline in tests for antidepressant activity.
Asunto(s)
Amitriptilina/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Piperidinas/farmacología , Amitriptilina/administración & dosificación , Amitriptilina/toxicidad , Animales , Antidepresivos/farmacología , Gatos , Evaluación Preclínica de Medicamentos , Electrocardiografía , Femenino , Hipotensión/inducido químicamente , Infusiones Parenterales , Masculino , Paroxetina , Piperidinas/administración & dosificación , Conejos , Convulsiones/inducido químicamente , Antagonistas de la Serotonina/farmacología , Taquicardia/inducido químicamenteRESUMEN
Cardiac arrhythmics were induced in conscious rabbits by intracardiac electric stimulation. The arrhythmic threshold remained constant for a period of more than 6 months. The antiarrhythmic drugs ajmaline, prajmalium, disopyramide, quinidine, lidocaine, propranolol and verapamil, given i.v. or orally, were screened for their threshold-raising potency. Particularly the membrane-stabilizing antiarrhythmics showed significant effects. The model may constitute a useful screen for such drugs in the conscious animal.