6.13:
Adrenergic Antagonists: Chemistry and Classification of β-Receptor Blockers
β-receptor blockers or β-adrenoceptor antagonists bind to β receptors and inhibit catecholamine-mediated sympathetic responses.
All β blockers are competitive antagonists but differ in characteristics such as adrenoceptor subtype affinity, lipophilicity, and α-blockade ability.
β blockers are categorized as either nonselective or selective.
The first β blocker was dichloroisoprenaline with partial agonist activity. Further research led to the development of propranolol, which was a pure antagonist but nonselective agent.
Next, propranolol analogs were further explored to obtain clinically effective drugs with β1-selectivity. For instance, practolol and atenolol are β1-selective.
Few selective β1 antagonists, like metoprolol, showed cardioselective actions.
Additionally, β blockers are also categorized generation-wise. The first generation includes older, nonselective molecules, while the second comprises cardioselective molecules.
The third generation includes newer drugs such as labetalol and carvedilol with additional α blocking or vasodilatory action. These drugs are therapeutically important in treating heart ailments and hemodynamic disorders.
6.13:
Adrenergic Antagonists: Chemistry and Classification of β-Receptor Blockers
β-adrenergic antagonists, or β-blockers, modulate the sympathetic nervous system by targeting β-adrenoceptors and inhibiting catecholamine-mediated sympathetic responses. β-blockers differ in their adrenoceptor subtype affinity, lipophilicity, and α-blocking capabilities. The history of β-blocker development began with the prototype, dichloroisoprenaline, which exhibited partial agonist activity. As a result, propranolol was developed as a pure antagonist but nonselective agent, paving the way for more targeted therapies. The introduction of β1-selective drugs, such as practolol, atenolol, and later metoprolol, led to the development of cardioselective β-blockers.
Categorizing β-blockers generation-wise helps differentiate between the older, nonselective molecules of the first generation and the cardioselective molecules of the second generation. First-generation β-blockers include nonselective agents like propranolol, while second-generation drugs are characterized by their cardioselectivity, as seen in drugs like atenolol and metoprolol. The clinical significance of β-blockers extends to those with additional α-blocking properties, which offer a unique combination of effects. These dual-action drugs, such as carvedilol and labetalol, offer therapeutic benefits in managing hypertension and heart failure by simultaneously targeting both α- and β-adrenergic receptors.
To summarize, β-blockers play a vital role in modulating the sympathetic nervous system through their diverse characteristics and modes of action. From their early beginnings with dichloroisoprenaline to the development of cardioselective agents, β-blockers have evolved to provide tailored therapeutic benefits across various medical conditions.