[Animal experimental studies on the pharmacology of a new anti-arrhythmic of the imino-cycloheptane series, stirocainide].

: The action of 2- benzal -1-(2'-diisopropyl-amino-ethoxy-imino)- cycloheptane hydrogenfumarate ( Stirocainide , Th 494) has been investigated on isolated guinea-pig atria and papillary muscles and on the circulation of the anaesthetized and conscious cat. Th 494 is characterized as a Na+-inhibitory antiarrhythmic agent in isolated atria and papillary muscles. 1-10 mumol/l Th 494 induces only a small increase in action potential duration in both preparations, whereas no change in resting potential or amplitude of the action potential is observed. The action on the maximal rate of rise of the action potential (Vmax) depends on the rate of stimulation ("use-dependence"), this effect being somewhat smaller in atria as compared to papillary muscles. The increase in threshold of alternating current induced arrhythmias and in functional refractory period is also smaller in atria. Isometric force of contraction is reduced by Th 494 in guinea-pig atria and papillary muscles to a greater extent than in rabbit and cat. In the anaesthetized cat 2 mg/kg Th 494 i.v. induces a transient decrease in heart rate and a decrease in the maximal rise of left ventricular pressure. In addition, 4 mg/kg i.v. induces a transient decrease in systolic and diastolic blood pressure as well as a broadening of the QRS complex in the ECG. High doses of 4 and 8 mg/kg, respectively, lead to arrhythmias and apnoea, 8 mg/kg to exitus. Atropine does not influence the action of Th 494. 2 and 4 mg/kg Th 494 do not alter the action of norepinephrine on heart and circulation.(ABSTRACT TRUNCATED AT 250 WORDS)