LABETOLOL Synthesis, SAR, MCQ,Structure,Chemical Properties and Therapeutic Uses

LABETOLOL Synthesis, SAR, MCQ,Structure,Chemical Properties and Therapeutic Uses

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

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 328.4 g/mol
2 Physical appearance Solid
3 Melting point 188°C
4 Solubility Water solubility is 3.56e-04 M
5 Octanol/water partition coefficient 2.7
6 Presence of ring Benzene
7 Number of chiral centers 2

 

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.

i. Atenolol A. (±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
ii. Labetolol B. (RS)-2-Hydroxy-5-[1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl]benzamide
iii. Bisoprolol C. (RS)-1-{4-[(2-Isopropoxyethoxy)methyl]phenoxy}-

3-(isopropylamino)propan-2-ol

iv. Carvedilol D. (RS)-2-{4-[2-Hydroxy-3-(propan-2-ylamino)propoxy]phenyl}acetamide.

 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

[1] Carey B, Whalley ET. β‐Adrenoceptor agonist activity of labetolol on the isolated uterus of the rat. British journal of pharmacology. 1979 Sep;67(1):13-5.

[2] Lemke TL, Williams DA, Foye WO. Principles of medicinal chemistry. Williams & Wilkins; 2017, 356.

[3] Vardanyan R, Hruby V. Synthesis of essential drugs. Elsevier; 2006 Mar 10.

 

 

 

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