Paper
A survey of the pharmacological properties of metoprolol in animals and man.
Published Mar 13, 2009 · B. Åblad, K. Borg, E. Carlsson
Acta pharmacologica et toxicologica
135
Citations
2
Influential Citations
Abstract
: Studies in both animals and man have shown that metoprolol is a β1-selective adrenergic receptor antagonist devoid of betamimetic activity. The cardiac stimulant effect of isoprenaline is markedly inhibited by metoprolol in doses that only slightly influence the vasodilator and bronchodilator effects of isoprenaline. Metoprolol markedly inhibits the cardiac response to exogenous or neuronally released noradrenaline. This action is probably the main determinant of the acute general hemodynamic effects of the compound. Metoprolol differs from propranolol in being a very weak inhibitor of the peripheral vasodilator effect of adrenaline. The two blockers may therefore produce differential hemodynamic effects in situations in which endogenous adrenaline contributes to cardiovascular control. Metoprolol has a preventive antihypertensive action in rats with genetically determined hypertension. This effect is associated with an impaired vasoconstrictor fibre control, the mechanism of which is discussed. The results of the toxicological and general pharmacological studies indicate that metoprolol is a highly specific β-blocker. The pharmacokinetic studies indicate that metoprolol is completely absorbed after oral administration. The first pass elimination in man is about 55% and independent of dose in the therapeutic dose range. Metoprolol is eliminated from human blood plasma with a half-life of 3–4 hours. The main metabolites have been isolated and characterized pharmacologically. Unchanged metoprolol appears to be responsible for the β-blocking action. The pharmacological characterization of metoprolol gave results that warranted reformulation of the β1—β2-receptor classification of Lands et al. (1967). This modified adrenergic β-receptor concept is described and its implications are discussed.
Highly CitedMetoprolol is a highly specific -blocker with a preventive antihypertensive effect in rats with genetically determined hypertension, and its pharmacokinetics show a half-life of 3-4 hours.
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