Evaluation of partial β‐adrenoceptor agonist activity

Abstract

A partial β‐adrenoceptor (β‐AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a β‐AR agonist with higher intrinsic activity. In vivo partial β‐AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (β1/β2), inotropicity (β1) or peripheral vasodilatation and finger tremor (β2). β‐AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, β‐AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (β1) and potassium (β2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a β‐adrenoceptor blocker with partial β1‐AR agonist activity compared with a β‐adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using β‐AR blocking drugs with partial β1‐AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between β2‐AR partial agonist activity and endogenous adrenergic activity. For predominantly β2‐AR agonists such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly β2‐AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. β2‐AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether this phenomenon is relevant in the setting of acute severe asthma.