Although beta-blockers were introduced into clinical medicine 30 thirty years ago, controversy continues as to the optimal pharmacodynamic profile of such agents. This commentary reviews the development of beta-blockers with partial agonist properties in the context of a recent study on epanolol. The influence of partial agonism on the efficacy and tolerability of beta-blockers is summarized, and it is concluded that, in general, there is little convincing evidence from controlled clinical studies that partial agonism confers significant clinical benefit over full antagonists.

Despite the fact that beta blockers were introduced into clinical practice 25 years ago, new beta blockers with differing kinetic and dynamic profiles continue to be developed and marketed. This overview assesses some of the more extensively studied agents from the point of view of proof of utility and the validity of claims for therapeutic advances. The clinical data suggests that despite the expectations of improvements based on kinetic and dynamic consideration, none of the newer agents have been shown unequivocally, either in terms of efficiency or tolerability, to be an advance over the reference agents, the beta 1 antagonists atenolol and metoprolol. This may be either because such improvements will not occur or because of shortcomings in the design and duration of comparative studies. There are trends to suggest that celiprolol has lesser effects on bronchial function and that it has a lesser impact on lipoprotein profiles. Approaches are suggested that might enable clinicians to appraise for themselves the validity of claims for the improved efficiency of new beta blockers.

ABSTRACT. Beta adrenoceptor antagonists are effective in the symptomatic management of angina pectoris. This paper examines critically the possible influence of the ancillary properties of β1 selectivity, partial agonism and membrane‐stabilizing action on the response in anginal patients. The response is categorized according to experimental, pharmacological and clinical end‐points, placing emphasis on the possible errors which may arise from extrapolation from the former to the latter. It is concluded: That selective beta adrenoceptor antagonism confers limited, but tangible advantages over non‐selective antagonists in regard to patients with reversible airways obstruction, and also in the metabolic and haemodynamic response to acute hypoglycaemia. Cardioselectivity does not influence the central haemodynamic response to exercise, but lessens adrenaline‐mediated hypertensive responses to smoking and hypoglycaemia. Non‐selective partial agonists cause less reduction in resting ventricular function, but their effects on cardiac output during exercise are indistinguishable from full antagonists. Membrane stabilizing properties have a marked influence on the tolerability of these agents in terms of unwanted, nonspecific central nervous system symptoms. Unresolved questions relate to the influence of partial agonism on fatigue, metabolic responses, especially blood lipids and glucose, and the possibility of lesser efficacy in angina compared to full antagonists.