5.3 Project initiation

In the early 1970s a discovery was made independently by two different researchers, Klaus Starke in Germany and Salomon Langer in Argentina. Their results showed that there were two types of alpha receptor. The first type, which they called alpha₁ is the one already described that is found on the blood vessel wall. The second type, which they called alpha₂, is located on the nerve-ending itself. Noradrenaline binds to the alpha₂ receptors when the alpha₁ receptors are saturated, thereby inhibiting further release of noradrenaline from the nerve-endings. Most importantly, the alpha₂ receptors probably have a different shape from the alpha₁ receptors and may well interact in a different way with the noradrenaline molecule.

Dr Michael Davey realised that this could provide an explanation of the unusual pharmacological properties displayed by prazosin. He and his co-workers were soon able to show that prazosin was a potent, highly selective, alpha₁-blocker, and interacted only very weakly, if at all, with the alpha₂ receptor. In contrast, many of the old alpha₁-blockers could block both types of receptor thus allowing continued release of noradrenaline, an effect which soon overcame the ability of these drugs to reduce blood pressure. Clearly this new insight satisfied the third criterion of an understanding of the pharmacological mechanism and the fourth requirement, a chemical starting point, was provided by prazosin itself. Here then was the necessary scientific basis to allow the design of an improved drug, one that would only need to be taken once a day.