Xylometazoline

IUPAC nomenclature

2-[(4-tert-butyl-2,6-dimethylphenyl)methyl]- 4,5-dihydro-1H-imidazole.

Classification

Xylometazoline is an α₁-adenergic agonist.

Physiochemical Properties

Mechanism of Action

i. Xylometazoline acts on α-adrenergic receptors in arteriols and mucosa.

ii. Systemic vasoconstriction due to activation of adrenal system.

iii. Decrease in blood flow and hence, decreased nasal congestion due to this.

Structure Activity Relationship

• Primary or secondary aliphatic amine separated by two carbons from a substituted benzene ring is essential for the high agonist activity.
• The hydroxyl substituted carbon must be in the R configuration for the maximal direct activity.

R¹ substitution:

• When R¹ is increased in size, activity of alpha receptors decreases and activity of the beta receptors increases
• Activity of both alpha and beta receptors is maximum when R¹ is methyl group.
• Alpha agonist activity decreases when R¹ is larger than methyl, and went negligible when R¹ is isopropyl.
• Large lipophillic groups can afford compounds with alpha blocking activity.
• N-substituent provides selectivity for different receptors.
• Arylalkyl group can provide beta selectivity, increased cell penetration and increased lipophillicity for the longer duration of action.

R² substitution:

• Ethyl group can eliminate the alpha activity of the drug.
• Erythrostero isomers have maximal activity.
• The additional methyl group makes the drug more selective for the alpha₂

R³ substitution on the aromatic ring:

• 3’,4’-dihydroxy substituted benzene ring has poor oral activity.
• 3’, 5’-dihydroxy compounds are orally active.
• At least one of the groups is required which can form hydrogen bonds. And if only one group is present then it is preferred at 4’ position to retain the beta₂
• If phenyl group has no phenolic substituent then it may act directly or indirectly.[2]

Method of synthesis

i. Chloromethylation of 1-tert-butyl-3,5-dimethylbenzene.

ii. Transformation of the chloromethy derivative into a nitrile.

iii. Reaction of the above formed compound with ethylenediamine gives xylometazoline.

Therapeutic Uses

Xylometazoline is used for the treatment of stuffy nose due to allergies, common cold or sinus irritation.

Side Effects

Common side effects of xylometazoline are

• dryness
• burning inside the nose; sneezing and runny nose.

Other side effects are

• wheezing,
• shortness of breath,
• light headedness,
• pounding heartbeats,
• headache dizziness and nervousness.

MCQs

Q.1 “2-[(4-tert-butyl-2,6-dimethylphenyl)methyl]- 4,5-dihydro-1H-imidazole” is the IUPAC nomenclature of which drug?

a) Xylometazoline

b) Triptorelin

c) Isoproterenol

d) Clonidine

Q.2 Number of rings present in the structure of Xylometazoline?

a) 1

b) 2

c) 3

d) 4

Q.3 Match the following with correct classifications of the drugs.

 a) i-A, ii-D, iii-B, iv-C

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

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

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

Q.4 Correct steps for the mechanism of action of the drug Xylometazoline.

I. Activation of adrenal system

II. Action on α-adrenergic receptors in arteriols and mucosa

III. Systemic vasoconstriction

IV. Decrease in blood flow and hence, decreased congestion.

a) I – II – IV – III

b) III – II – IV – I

c) II – I – III – IV

d) IV – I – III – II

Q.5   Correct sequence for True and False for the given statements related with the SAR of drug Xylometazoline?

• When R¹ is increased in size, activity of alpha receptors decreases and activity of the beta receptors increases
• At least one of the groups is required which can form hydrogen bonds. And if only one group is present then it is preferred at 4’ position to retain the beta₂ activity
• Activity of both alpha and beta receptors is maximum when R¹ is methyl group.
• Primary or secondary aliphatic amine separated by two carbons from a substituted benzene ring is essential for the high agonist activity.

a) TTFT

b) TTTF

c) TFTF

d) TTTT

Q.6 Cyclization of 2-(4_tert-butyl-2,6-dimethylphenyl)acetonitrile with ethylene diamine will give?

a) Oxymetazoline

b) Tetrahydrozoline

c) Xylometazoline

d) Tizanidine

 Q.7 The drug  Xylometazoline is mainly used as?

a) Anticancer drug

b) ANticonvuslive drug

c) Antiseptic

d) Nasal decongestant

For More Standard and Quality Question Bank you can Join Our Test Series Programme for GPAT, NIPER JEE, Pharmacist Recruitment Exam, Drug Inspector Recruitment Exams, PhD Entrance Exam for Pharmacy

Participate in Free GPAT MOCK Test

ANSWERS

1-a

2-b

3-b

4-c

5-d

6-c

7-d

REFERENCES