Pharmacological investigation of a new anti-arrhythmic agent, GYKI-23 107.

GYKI-23 107 is a new antiarrhythmic substance with local anaesthetic activity. Its specific pharmacological and cardiovascular effects were studied in vivo and its efficacy was compared with that of lidocaine and mexiletine. GYKI-23 107 was effective against chemically (aconitine and ouabain) induced arrhythmias after both parenteral and oral administration. In aconitine-induced arrhythmia in mice the new compound was more active than either mexiletine or lidocaine after i.p. treatment. In ouabain-induced arrhythmia in dogs, the ED50 of GYKI-23 107 was approximately half that of mexiletine after i.v. injection. GYKI-23 107 and mexiletine produced similar elevation of the fibrillation threshold in anaesthetized cats. After oral pretreatment, GYKI-23 107 showed protective effects against coronary ligation-induced arrhythmia in conscious rats. The circulatory side-effects of GYKI-23 107 in anaesthetized and conscious dogs and cats were milder then those of mexiletine. In the antiarrhythmic dose range there were no adverse cardiovascular actions.