Labetolol

IUPAC nomenclature

(RS)-2-Hydroxy-5-[1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl]benzamide.

Classification

Labetolol is a mixed α/ß blocker.

Physiochemical Properties

Mechanism of Action

• Labetolol selectively antagonizes α₁– adrenergic receptors and it nonselectively antagonizes ß-adrenergic receptors.
• It has having 3 times ß-blocking activity than α-blocking activity.
• Antagonism of α-receptors leads to vasodilation and decreased vascular resistance, which further results in decreased blood pressure.
• Antagonism of ß₁-adrenergic receptors produces slight decrease in heart rate.
• Antagonism of ß₂-adrenergic receptors is responsible for the side effects of the drug like bronchospasms.
• Labetolol produces a sustained vasodilation for a longer duration without the significant lowering in cardiac output or stroke volume, and a slight decrease in heart rate.

Structure Activity Relationship

• The type of N-substitutions such as N-isopropyl and N-t-butyl eliminates α₁-activity.
• Arylalkyl groups with α-methyl substituent returns back the α­₁-affinity but not the intrinsic activity.
• The ß-blocking activity is almost 1.5 folds that of its α₁-blocking activity.

Method of synthesis

i. N-alkylation of N-benzyl-N(4-phenyl-2-butyl)amine 5-bromoacetylsalicylamide forms aminoketone.

ii. Debenzylation of aminoketone by hydrogen using palladium-platinium on carbon catalyst yields labetolol.

Therapeutic Uses

Labetolol is used for treatment of:

• Hypertension
• Prevention of strokes
• Prevention of heart attacks
• Prevention of kidney problems

Side Effects

Side effects of Labetolol are:

• Dizziness
• Tiredness
• Scalp tingling
• Decreased libido
• Lightheadedness

MCQs

Q.1 Choose the correct option related to the correct physicochemical properties of drug labetolol.

I. Molecular weight is 266.34 gm/mol.

II. It is present in solid form.

III. Melting point is 188°C

a) I, II, III

b) II, III

c) I, III

d) I, II

Q.2 Match the following of the drugs with their correct IUPAC names.

 a) i-B, ii-A, iii-C, iv-D

b) i-D, ii-A, iii-B, iv-C

c) i-A, ii-C, iii-D, iv-B

d) i-D, ii-A, iii-C, iv-B

Q.3 Pick the correct statement related with the mechanism of action of drug labetolol?

 a) It selectively antagonizes α₁-adrenergic receptors and nonselectively antagonizes ß-adrenergic receptors .

b) It nonselectively antagonizes α-adrenergic receptors and nonselectively antagonizes ß-adrenergic receptors .

c) It selectively antagonizes α₂-adrenergic receptors and selectively antagonizes ß₂-adrenergic receptors .

d) It nonselectively antagonizes α-adrenergic receptors and nonselectively antagonizes ß-adrenergic receptors .

Q.4 Correct sequence for True/false for the classification of the drug can be?

• Atenolol: selective ß₁-adrenergic antagonist.
• Labetolol: mixed α/ß blocker
• Salmeterol: nonselective adrenergic agonist.
• Methyldopa: nonselective α-adrenergic antagonist

a) TTFF

b) TTFT

c) TFTF

d) FFTT

Q.5 Complete the following sentence related with structure activity relationship of Labetolol-

‘The ß-blocking activity is almost ………. That of α-blocking activity.

a) Half

b) Quarter

c) Double

d) 1.5 folds

Q.6 The correct sequence for the steps for synthesis of drug Labetolol from N-benzyl-N(4-phenyl-2-butyl)amine 5-bromoacetylsalicylamide

I. N-alkylation

II. Debenzylation

III. Hydrolysis

 a) I – II

b) III – II

c) II – I

d) II – III

Q.7 Side effect of drug Labetolol?

a) Lightheadedness

b) scalp tingling

c) Decreased libido

d) All of the above

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ANSWERS

1-b

2-d

3-a

4-a

5-c

6-a

7-d

REFERENCES