Methacholine

IUPAC nomenclature

2-(Acetyloxy)-N,N,N-trimethylpropan-1-aminium.

Classification

Methacholine is a cholinergic agonist falls in the class of choline esters.

Physiochemical Properties

Mechanism of Action

• Methacholine induces bronchoconstriction by agonizing the muscarinic receptors.
• Therefore, this is used during the test of asthma and bronchial hyperreactivity.

Structure Activity Relationship

• When the nitrogen of the quaternary ammonium group is replaced with arsenic, phosphorous, sulfur or selenium, their activity decreases.
• It is necessary for the atom present at the nitrogen position to have a positive charge to have muscarinic activity.
• When all three methyl groups are replaced by larger alkyl groups at the quaternary nitrogen, drug becomes inactive as agonist.
• When all the methyl groups associated with the quaternary nitrogen atom are replaced by ethyl groups, the compound becomes cholinergic antagonist.
• Replacement of just one methyl group associated with quaternary nitrogen with an ethyl or a propyl group gives the compound which is having lesser activity than acetylcholine.
• Substitution of the methyl groups associated with quaternary nitrogen with hydrogen atoms also leads to diminishing of the muscarinic activity.
• At the ethylene bridge, synthesis of acetic acid esters of quaternary ammonium alcohols of greater length than choline led to a series of compounds which are having lesser activity as the length of the chain increases.
• There should be no more than 5 atoms between nitrogen and terminal hydrogen to have the maximum muscarinic activity.
• Replacement of the ethylene bridge by the alkyl groups larger than methyl groups decreases the activity.
• The R-(-) isomer is 20 time less potent.
• For the maximum potency, the alkyl groups at the nitrogen atoms should not be larger than methyl groups.
• Presence of oxygen in an ester form increases the activity.
• For maximum activity, there should be two- carbon atoms between the nitrogen and oxygen atom. [1]

Method of synthesis

i. Addition of trimethylamine to propylene chlorohydrins gives (2-hydroxypropyl)trimethylammonium ion.

ii. The latter compound on reaction with acetic anhydride forms methacholine.

Therapeutic Uses

Methacholine is used for test of:

• Asthma
• Bronchial hyperreactivity

Side Effects

Side effects of methacholine are:

• Dizziness
• Nausea
• Vomiting
• Lightheadedness
• Sore throat
• Headache

MCQs

Q.1 Correct statements related with the Physicochemical properties of Methacholine are?

I. Molecular weight = 160.23 gm/mol

II. Physical appearance : present in viscous liquid form

III. Melting point = 35°C

IV. Solubility: very soluble in water 

a) I, III

b) I, II, IV

c) II, IV

d) I

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

 a) i-B, ii-A, iii-D, iv-C

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

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

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

Q.3 Correct steps for the mechanism of action of the drug Methacholine?

I. Antagonizing muscarinic receptors

II. Agonizing muscarinic receptors

III. Induction of bronchoconstriction

a) I – III

b) II – III

c) III – I

d) III – II

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

• Methacoline: Cholinergic antagonist
• Procyclidine: Muscarinic antagonist
• Homatropin: Cholinergic agonist
• Atropin: Muscarinic antagonist

a) FTFT

b) TTTF

c) TFTF

d) FFTT

Q.5 Number of atoms requires between nitrogen and terminal hydrogen to have maximum activity for Methacholine is?

a) 1

b) 4

c) 5

d) 7

Q.6 The correct sequence for the steps for synthesis of drug Methacholine from Propyline chlorohydrine?

I. Reaction with trimethylamine

II. Reaction with acetic anhydride

III. Reduction

IV. Oxidation

a) I – II

b) I – III – II

c) I – III – II – IV

d) III – II – IV

Q.7 Side effect of drug Methacholine?

a) Dizziness

b) Sore throat

c) Lightheadedness

d) All of the above

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ANSWERS

1-d

2-b

3-b

4-a

5-c

6-a

7-d

REFERENCES