β-Adrenoceptor Blocking Agents

Abstract

The idea of different adrenergic receptors originated with Langley in 1905. He suggested that the receptors contained inhibitory and excitatory receptor substances. Sir Henry Dale (1906) observed the next year that while the excitatory actions of adrenaline were blocked by ergot, the inhibitory ones were not, providing evidence for two types of adrenergic receptors. Then in 1948 Ahlquist published his now classical paper in the American Journal of Physiology where he studied the effect of six sympathetic stimulating drugs and revealed two patterns of response. He termed one pattern the α effects which included vasoconstriction, here adrenaline was most potent, followed by noradrenaline. Secondly there were β effects which included smooth muscle relaxation and cardiac stimulation. Isoprenaline was the most active here, adrenaline was third, and noradrenaline least effective (Ahlquist 1948). The adrenergic receptors have subsequently been further divided into α₁, α₂, ß ₁ and ß ₂ receptors (Lefkowitz 1976; Williams and Lefkowitz 1978; Lees 1981; Andersson 1982). The first report of ß adrenoceptor blocking activity came in 1958 when the properties of dichloroisoprenaline were discovered in animal experiments. This drug had powerful intrinsic sympathomimetic activity and while its importance as a pharmacological tool was recognized the therapeutic potential of this new approach was not (Moran and Perkins 1958; Powell and Slater 1958).