Adalat: Historical Aspects from the Cardiologist’s View

Abstract

The discovery of the principle of calcium antagonism by Reckenstein in the mid-1960s [1] has to be regarded as a major breakthrough especially for the therapy of ischemic heart disease. Nifedipine (Adalat), developed by Bayer Pharmaceutical Company in the mid-1960s [2, 3] was recognized by Fleckenstein as a very potent calcium antagonist soon afterwards [4]. This first clinically applicable dihydropyridine not only proved to be very effective in protecting myocytes from calcium overload [4], but also in relaxing vascular smooth muscle cells through blockade of the voltage-dependent calcium channel [5]. Hence, it became evident already in the late 1960s and early 1970s [2] that the drug could play an important role in the medical treatment of coronary heart disease; particularly the vasorelaxing properties became very important, as nifedipine was found to actively increase coronary flow in ischemic areas, and especially in the subendocardial layers [6], without disturbing autoregulation or leading to a steal phenomenon [7]. Hence, in the late 1960s and early 1970s studies were undertaken to analyze its anti-ischemic effect in man, either by analyzing ST segment changes during exercise [8], or by measuring transmural coronary blood flow in ischemic areas in patients with coronary artery disease [2, 7].