β – Adrenergic blocking agents

1. Aryl ethanolamines – Isoproterenol, pronethalol, Dichloro

isoproterenol
2. Aryloxy propanolamines – Propranolol, Practalol, Metaprolol,
Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol.
III. Both α and β – Adrenergic blocking agents
Labetalol, Carvedilol.
These drugs block the effects of Endogeneous and exogeneous catecholamines.
These drugs slow the heart rate and decrease the force of contraction. They
competitively inhibit β – Adrenergic receptors. These are also used in the treatment
of hypertension, arrhythmiasis, coronary artery disease and open angle glaucoma.

III. Both α and β – Adrenergic blocking agents

Carvedilol
SAR for Beta blockers

1. The O-CH2 group between aromatic ring and the ethylamino side chain is
responsible for the antagonistic property.
2. Replacement of catechol hydroxyl group with chlorine or phenyl ring retains the
beta blocking activity.
3. N,N- di substitution decrease beta blocking activity. Activity is maintained when
phenylethyl, hydroxyl phenyl ethyl or methoxy phenyl ethyl groups are added to
amine as a part of molecule.
4. The two carbon side chain is essential for the activity.
5. Nitrogen atom should be of secondary amine for optimum beta blocking activity.
6. The carbon side chain having hydroxyl group must be S- configuration for
optimum affinity to beta receptor.(Ex- Levobunolol, Timolol).
7. The aryloxy propanolamines are more potent than aryl ethanolamines.
8. Replacement of ethereal oxygen in aryloxy propanolamines with S, CH2 or N-CH3
is decreased the beta blocking activity.
9. The most effective substituents at amino group is isopropyl and tertiary butyl
group.
10. The aromatic portion of the molecules could be varied with good activity.
11. Converting the aromatic portion to phenanthrene or anthracene decrease the
activity.
12. Cyclic alkyl substituents are better than corresponding open chain substituents at
nitrogen atom of amine.
13. Alpha methyl group at side chain decrease activity.

Mechanism of action
1. These drugs competitively inhibit the adrenergic receptors.
2. Beta antagonists are invariably employed in the treatment of essential
hypertension and cause an effective decrease in BP by exerting direct effect on
heart and blood vessels, minimizing sympathetic outflow from CNS and affecting the
rennin-angiotensin- aldosterone system.
3. Some drugs like propranolol precipitate an asthmatic attack by antagonizing beta-
2 receptors in bronchial smooth muscle and give rise to sudden contraction of
bronchial smooth muscle.