INTERACTIONS BETWEEN VERAPAMIL AND METOPROLOL IN THE DEVELOPING CHICK-EMBRYO HEART

A calcium blocking agent, verapamil, and a beta-1-adrenoreceptor blocking agent, metoprolol, were administered alone or in combination to 4-day-old chick embryos (Hamburger-Hamilton developmental stage 24). Embryos co-administered with verapamil (0.05 nmol) and metoprolol (0.1 or 1.0 nmol), neither of which alone caused significant teratogenicity, showed cardiovascular malformations, including ventricular septal defects associated with or without dextroposition of the aorta (overriding aorta). The alteration of calcium movement into the myocyte and/or the haemodynamic change following impaired calcium transport are suggested to be possible causative factors.