Mechanism of Action of Isoprenaline
Isoprenaline is a potent nonselective beta-adrenergic agonist with very low affinity for alpha-adrenergic receptors, acting on both β1 and β2 receptor subtypes to produce cardiovascular effects. 1
Receptor Pharmacology
Isoprenaline stimulates β1-adrenoceptors in the heart, producing positive chronotropic (increased heart rate) and positive inotropic (increased contractility) effects. 1, 2
The drug also activates β2-adrenoceptors, which mediate peripheral vasodilation, bronchodilation, and contribute to cardiac effects, particularly during stress conditions. 2, 3
Unlike norepinephrine or epinephrine, isoprenaline has virtually no alpha-adrenergic activity, making it a pure beta-agonist. 1
Cardiovascular Effects Through Beta-Receptor Activation
Direct Cardiac Effects (β1-mediated)
β1-receptor stimulation in the heart increases myocardial contractility, accelerates heart rate, and enhances cardiac conduction. 1, 2
In human atrial and ventricular tissue, both β1 and β2 receptors contribute to positive inotropic effects, though β1 stimulation produces maximal contractile force increases while β2 stimulation produces only submaximal increases in ventricular muscle. 2
The chronotropic effect of isoprenaline is mediated approximately equally by β1 and β2 receptor stimulation, as demonstrated by equal antagonism with selective β1 and β2 blockers in healthy volunteers. 2
Peripheral Vascular Effects (β2-mediated)
Isoprenaline lowers peripheral vascular resistance primarily in skeletal muscle, renal, and mesenteric vascular beds through β2-receptor activation. 1
This vasodilation decreases diastolic blood pressure while systolic pressure may remain unchanged or rise, resulting in a typical fall in mean arterial pressure. 1
Cardiac output increases due to the combination of positive inotropic and chronotropic effects occurring against diminished peripheral vascular resistance. 1
Coronary and Pulmonary Effects
Isoprenaline relaxes bronchial smooth muscle through β2-receptor stimulation, preventing or relieving bronchoconstriction, though tolerance develops with overuse. 1
The drug produces pulmonary artery vasodilation, but clinical utility is limited by tachycardia and systemic vasodilation. 4
Metabolic and Other Effects
Isoprenaline stimulates the release of free fatty acids and energy production equally to epinephrine, but causes less hyperglycemia than epinephrine. 1
The drug is metabolized primarily by catechol-O-methyltransferase (COMT) in the liver and other tissues. 1
Isoprenaline is a relatively poor substrate for monoamine oxidase (MAO) and is not taken up by sympathetic neurons to the same extent as epinephrine and norepinephrine, resulting in a longer duration of action than epinephrine, though still brief. 1
Critical Mechanistic Considerations
The increase in myocardial oxygen demand through β1 effects occurs simultaneously with decreased coronary perfusion through β2-mediated vasodilatory effects, creating an unfavorable myocardial oxygen supply-demand balance. 5, 4
In situations of high circulating catecholamines or stress, β2-adrenoceptor stimulation contributes additional increases in contractility and heart rate beyond baseline β1-mediated regulation. 2
Under normal physiologic conditions, contractility and heart rate are regulated only by cardiac β1-adrenoceptors, with β2 receptors becoming functionally important primarily during stress states when large amounts of circulating catecholamines are present. 2