Long before their merger in 1999, Astra and Zeneca (formerly Imperial Chemical Industries - ICI) established a common heritage in the cardiovascular area as pioneers of beta-blockade. Unknown to each other, ICI and Astra initiated projects in the late 1950s focusing on blockade of beta-receptors as a potential approach to the treatment of cardiac disease 47,48 . The resulting research and development programmes led to the launch by ICI of the first clinically viable beta-blocker, propranolol (InderalTM ) in 1965, followed soon after (1967) with the launch of alprenolol (AptinTM ) by Astra. Subsequent research at Astra focused on achieving greater selectivity for the β1 -receptors (cardioselectivity), resulting in the development of Seloken® /Seloken ZOK® (metoprolol/metoprolol CR/XL).
Start by understanding the biology
An important characteristic of the development of beta-blockers was a strong foundation in basic research into cardiac physiology, and the seminal role of collaborators from academic institutions. It was the Nobel Laureate, Sir James Black, then a lecturer at the University of Glasgow, who suggested to ICI that coronary artery disease might be treated by blocking the action of adrenaline on the heart. This suggestion was based on the hypothesis that increased catecholamine secretion in response to stress leads to an increase in the work of the cardiac muscle, and hence cardiac oxygen demand, without an increase in oxygen supply. Hence, a treatment for coronary artery disease might be based on reducing cardiac oxygen consumption, rather than increasing coronary blood flow.
Similarly at Astra, Arvid Carlsson, also a future Nobel Laureate, advised a radical approach to the young company, which was seeking to develop a new antiarrhythmic: ”Instead of restricting the project’s goals to the symptom heart rhythms, I would study the mechanisms that control the activities of the heart. By studying the factors that control the heart rhythm and the work of the heart muscle you can hope to develop medicines for different heart diseases” 47 .
Nobel Laureates Sir James Black and Arvid Carlsson played key roles in guiding ICI (Zeneca) and Astra, respectively, towards the development of clinically useable beta-blockers.
