text: The β-blockers are an immensely important class of drugs due to their high prevalence of use. The discovery of β-blockers reaches back to more than 100 years ago, when early investigators came up with the idea that catecholamines were binding selectively to receptor-like structures and that this was the cause of their pharmacological actions. In 1948, Raymond P. Ahlquist published a seminal paper concluding his findings, that there were two distinct receptors for catecholamine drugs, and they caused different responses in the heart muscle. He labeled them α-and β-adrenoceptors. These findings were soon to be a foundation for further research into drug development.
  In the early 1960s, James Black, a Scottish pharmacologist, and associates of his at the Imperial Chemical Industries (ICI) in Great Britain were working on a series of β-adrenergic blocking compounds, pronethalol and propranolol. Dr. Black focused on developing a drug that would relieve the pain of angina pectoris, which results from oxygen deprivation in the heart. His plan was to create a drug that would decrease the hearts requirement for oxygen. He hypothesized that these compounds would lower the hearts oxygen consumption by interfering with the effects of catecholamines. In 1958, the pharmacological properties of dichloroisoproterenol (DCI) were described, a β-antagonist discovered a few years before by the Eli Lilly group. It was the synthesis of DCI which established that β-receptors could be chemically blocked and thus its existence could be confirmed. DCI had no clinical utility but a replacement of the 3,4-dichloro substituents, with a carbon bridge to form a naphtylethanolamine derivative, afforded a clinical candidate, pronethalol.
  In April 1963, toxicity tests for pronethalol showed results of thymic tumours in mice. Nevertheless, it was launched under the trade name Alderlin, as the first clinically useful β-blocker. The launch took place in November 1963 when many small-scale clinical trials had proved their effectiveness in angina and certain types of arrhythmias. Pronethalol was only marketed for use in life-threatening situations. Dr. James Black went on to create another β-blocker, called propranolol; a non-selective β-blocker. Clinical trials started in the summer of 1964 and a year later, propranolol was launched under the trade name Inderal, only two and a half years after it had first been tested. It turned out to have a higher potency than pronethalol, with fewer side effects. Propranolol became the first major drug in the treatment of angina pectoris, since the introduction of coronary vasodilators, (such as nitroglycerin), almost 100 years earlier. Propranolol became a best-selling drug, used to treat a wide range of cardiovascular diseases such as arrhythmia, hypertension and hypertrophic cardiomyopathy.