Adrenergic antagonists (Adrenergic blocking agents)

Adrenergic antagonists (Adrenergic blocking agents)

By

Dr. N. C. Baruah

Autonomic Nervous System

• The autonomic nervous system controls the visceral functions of the body.

• It controls the arterial pressure, gastrointestinal motility, the secretion of the G. I. Tract, the urinary emptying functions, regulation of body temperature, sweating, respiration, controlling and adjusting of eye sight and many other visceral functions.

• The functions of the autonomic nervous systems are very fast.

Adrenergic antagonists

• The efferent autonomic signals are transmitted to the organs by two systems, the sympathetic and parasympathetic nervous system.

• The drugs which antagonize the actions of sympathetic nervous system are called adrenergic antagonists.

• They can be divided into two classes:

– Alpha adrenergic blocking agents

– Beta adrenergic receptor blocking agents.

Adrenergic antagonists

• As α-agonist initiates vaso-constrictions and used to raise blood pressure, so in opposite to it the α- adrenergic blocking agents are used to relax the blood vessel (capillary) and to reduce blood pressure.

• Therapeutically they are used as antihypertensive drugs.

• The α-blockers have no structural similarity to the neurotransmitters (NE) or the catecholamine's.

• They have diverse structures.

Nonselective α-blockers

• Tolazoline , Phentolamine are imidazoline derivatives .

• Neither of these two drugs are useful as antihypertensive , because of their nonselective blocking of both α-1 and α-2 receptor, and cause tachycardia. They also have vasodilator actions.

• They can be used in peripheral vasoconstrictions. Phentolamine is used in the treatment of hypertension associated to pheochromocytoma.

• Tolazoline

• Phentolamine

• Phenoxybenzamine

Nonselective α-blockers

• Phenoxybenzamine is a haloalkylamine.

• It blocks both alpha 1 &2 receptor irreversibly.

• But it has selective blocking action on the excitatory responses of smooth as well as heart muscles.

Selective α-blockers

• Prazosin (Minipress), terazosin (Hytrin) , doxazosin (cardura) are the quinazoline derivatives .

• They selectively block the α-1 receptors and are used in the treatment of hypertension.

• These drugs contain three components the quinazoline ring, the piperazines ring and an acyl group.

• The 4-amino group on the quinazoline ring is important for α-1 activity.

• Prazosin

• Terazosin

• Doxazosin

Selective α-blockers • Alfuzosin (Uroxatral) is a quinazoline derivative

but it does not have a piperazines moiety .

• It is more selective to α-1 receptor of the prostate gland and is used in BPH (Benign prostatic hyperplasia).

• Tamsulosin ( Flumax) is a non-quinazoline benzene sulphonamide.

• Both are used in BPH.

• Alfuzosin

• Tamsulosin

Selective α-2 blockers

• Yohimbine is an indole alkylamines alkaloid found in the bark of Pausinystalia yohimbe and Raulfia serpentina root.

• It is a competitive selective α-2 blocker.

• Corynanthine is a α-1 blocker.

• It differs from the Yohimbine only in the stereochemistry in one position.

• Mitrazapine is also a selective α-2 blocker, used as an anti-depreassant .

• Yohimbine

• Corynanthine

Beta blockers: Non selective beta blockers

• The β-blockers are the most widely used

antihypertensive.

• Propranolol (Inderal) blocks both β-1 & 2 receptors.

• It is used for various types of cardiac disorders. (Hypertension, Arrhythmia, Angina pectoris, myocardial infarction etc and in pheochromocytoma).

• Other nonselective blockers are Nadolol, Pindolol, Penbutolol, Carteolol, Sotalol.

• Propranolol

• Pindolol

• Penbutolol

• Sotalol

• Nadolol

• Carteolol

Β-1 selective blockers

• The 2nd generation drugs:

• Acebutolol (spectral),

• Atenolol (Tenormin),

• Betaxolol (Carlone),

• Bisoprolol (Zebeta),

• Metoprolol (Lopressor),

• Esmolol (Brevibloc).

• Acebutolol

• Atenolol

• Betaxalol

• Bisoprolol

• Esmolol

• Metoprolol

Β-blockers the 3rd generation

• The 3rd generation drugs have both α-and β- receptor blocking action:

• Labetalol( Normodyne),

• Carvedilol (Coreg) .

• These drugs have an aryl alkyl group for alpha activity and near to it a methyl group for beta activity.

• Carvedilol

• Labetalol

References

• Textbook of Medical Physiology , 11th edition, Guyton and Hall,748-760.

• Wilson & Gisvold’s Textbook of Organic Medicinal and Pharmaceutical Chemistry, 12th edition, 519-557.

• Burger’s Medicinal Chemistry & Drug Discovery, sixth edition, 1-38.

• Foye’s Principles of Medicinal Chemistry, 7th edition,340-364.