Derivatives of 1,3-benzodioxole, the preparation and use thereof

DETAILED DESCRIPTION OF THE INVENTION It has been surprisingly found that the compounds of the general formula I are very active for the treatment of heart arrhythmia.
Said compounds can be used for the treatment of various heart diseases such as premature heart contractions, ventricular and supraventricular tachycardias either idiopathic or subsequent to a cardiopathia or to a coronary disease, cardiac arrhythmias due to digitalin intoxication, as well as atrial fribrillation and flutter, particularly in the early stage.
It is known (see Koch-Weser, J.
Arch.
Int.
Med.
129; 763, 1972) that none of the presently available antiarrhythmic agents are satisfactory for the prophylaxis of tachycardias and fibrillation of ventricular origin.
The oral activity of the known antiarrhythmic agents, such as procainamide or lidocaine, is either too short leading to multiple day and night administration (for example with procainamide) or too low to be of some practical utility (for example with lidocaine) or their therapeutic activity is conjugated with frequent and dangerous side effects, such as hypotension (with procainamide), sudden death, agranulocytosis or idiosyncrasy.
The compounds of general formula I according to this invention are very active when orally administered, although they may also be administered parenterally.
They have also a long activity duration and are not depressant for the myocardial function.
Applicants do not know any orally active antiarrhythmic agents whith does not act at the same time as a depressant of the myocardial function.
The oral antiarrhythmic activity of the compounds of formula I has been proved by tests on rats using aconitine which is a compound causing premature heart contractions and death of the animals.
The method used for these tests is described hereafter: Animals Male or female rats with a body-weight ranging from 380 to 450 g.
Aconitine solution 3.
12 g aconitine nitrate/1 ml physiological saline.
Solution of the compound to be tested 0.
75% in distilled water