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

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

Doxylamine

IUPAC nomenclature

(RS)-N,N-dimethyl-2-(1-phenyl-1-pyridin-2-yl-ethoxy)-ethanamine

Classification

  • H1-receptor antihistamine
  • Ethanolamine ether antihistamine

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 270.37 g/mol
2 Physical appearance Clear colorless liquid
3 Melting point <25oC
4 Solubility Soluble in acids
5 Octanol/water partition coefficient 2.15
6 Presence of ring Pyridine, phenyl
7 Number of chiral centers 1

 

Mechanism of Action

  • It competitively inhibits histamine at H1-receptors
  • The drug also have sedative and anticholinergic effects

 

Structure Activity Relationship

Structure activity of ethanolamine ethers can be summarized as:

  • 8-chlorotheophyllinate salt of diphenhydramine is used for treatment of motion sickness
  • Compounds with p-Cl-Ph and 2-pyridyl aryl groups are carboxamine, which is a potent anti-histamine drug.
  • Substitution of the methyl group at the carbon alpha to the ether function gives a related compound known as doxylamine.
  • An additional carbon atom between oxygen and nitrogen produces clemastine which has lower sedative properties.
  • In setastine, alkyl amine substituent is incorporated into seven-membered hexahydroazepine ring, having lower sedative properties.
  • With increase in alkyl group size at C-2’, there is decrease in antihistaminic activity and increases in anticholinergic activity.
  • Introduction of alkyl substituents at C-4’results in decrease in anticholinergic activity and increase in antihistaminic activity.[1]

 

Method of synthesis

i. Reaction of 2-acetylpyridine and bromobenzene in presence of magnesium turning, tetrahydrofuran and toluene solvent to produce 2-pyridylphenylmethyl carbinol HCl.

ii. The above formed compound is reacted with 2-dimethylaminoethyl chloride hydrochloride in presence of potassium hydroxide and toluene solvent to get doxylamine.

iii. To produce doxylamine succinate, the last formed compound is treated with succinic acid in acetone solvent.[2]

Medicinal Uses

Doxylamine is used for treatment of:

  • Sneezing
  • Watery eyes
  • Hives
  • Runny nose
  • Skin rash
  • Itching
  • Hay fever
  • Cold symptoms
  • Allergy symptoms
  • Short-term insomnia 

 

Side Effects

Side effects of doxylamine are:

  • Hallucinations
  • Confusions
  • Dizziness
  • Drowsiness
  • Little urination
  • Blurred vision
  • Dry mouth and nose
  • Dry throat
  • Constipation
  • Allergic reactions
  • Difficulty in breathing
  • Swelling of face, throat, tongue, lips

  

MCQs

Q.1 Match the following with correct SAR of the ethanolamine ether antihistamine drugs-

i. 8-chlorotheophyllinate salt of diphenhydramine gives a drug knows as A. Dimenhydrinate
ii. Compounds with para-chlorophenyl groups and 2-pyridyl aryl groups are B. Clemastine
iii. An additional carbon atom between oxygen and nitrogen produces C. Setastine
iv. Alkyl amine substituent is incorporated into seven-membered hexahydroazepine ring to give D. Carboxamine

 a. i-D, ii-A, iii-C, iv-B

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

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

d.  i-A, ii-B, iii-D, iv-C

Q.2 Correct sequence for the True/False for correct IUPAC names of the drug can be?

  • Doxylamine: (RS)-N,N-dimethyl-2-(1-phenyl-1-pyridin-2-yl-ethoxy)-ethanamine
  • Dimethindene: N,N-Dimethyl-2-[3-(1-pyridin-2-ylethyl)-1H-inden-2-yl]ethan-1-amine
  • Isoxicam: 4-hydroxy-2-methyl-N-(5-methyl-1,2-oxazol-3-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
  • Meclofenamic acid: 2-[(2,6-dichloro-3-methylphenyl)amino]benzoic acid

a) TFFT

b) FFTT

c) FTFT

d) TTTT

Q.3 The correct physical appearance of doxylamine is?

a) Clear colorless liquid

b) Yellow oily liquid

c) White crystalline solid

d) Reddish-brown crystals

Q.4 Doxylamine inhibits?

a) H1 receptors

b) H2 receptors

c) Muscarinic receptors

d) Nicotinic receptors

Q.5 Which amongst the following is not a therapeutic use of drug Doxylamine?

a) Treatment of Bradycardia

b) Treatment of Allergic symptoms

c) Treatment of hay fever

d) Treatment of Runny nose

Q.6 Which of the following drug and their classification are correct?

I. Doxylamine: Ethanolamine ether antihistamine drug

II. Sevoflurane: Inhalational anesthetics

III. Bisoprolol: Alpha adrenergic blockers

IV. Lorazepam: Benzodiazepine sedative hypnotics

a) I, IV

b) I, II

c) II, III

d) III, IV 

Q.7 Doxylamine can be converted into Doxylamine succinate by reaction with?

a) Succinic acid in Acetone solvent

b) Succinic acid in NaOH solution

c) Oxalic acid in Acetone solvent

d) Oxalic acid in NaOH solution

 

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ANSWERS

1-c

2-d

3-a

4-a

5-a

6-b

7-a

 

REFERENCES

[1] Lemke TL, Williams DA, editors. Foye’s principles of medicinal chemistry. Lippincott Williams & Wilkins; 2012 Jan 24.

[2] Shrigadi N, Bodake M, Pradhan N. World Journal of Pharmaceutical Sciences.

 

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