Tolmetin        

IUPAC nomenclature

Classification

• Nonsteroidal anti-inflammatory drug

Physiochemical Properties

Mechanism of Action

• Prostaglandin synthetase enzyme is inhibited by tolmetin which lowers the plasma level of prostaglandin in man. This is responsible for the anti-inflammatory action of the drug.

Structure Activity Relationship

SAR of Tolmetin can be summarized as follows:

• Replacement of the 5-p-toluoyl group with p-chlorobenzoyl moiety have little changes on the activity of drug.
• 4-methyl-5-p-chlorobenzoyl analog is 4 times more potent then tolmetin.
• Substituting the chloro group with the p-methyl group blocks the oxidative metabolism which increases the duration of action by 1 day.
• Propionic acid analogue is less potent.

Method of synthesis

i. 1-methylindole is aminomethylated using formaldehyde and dimethylamine to form 2-dimethylaminomethyl-1-methylindol.

ii. Last is methylated by methyl iodide to produce the corresponding quarternary salt.

iii.Eaction of the above formed compound with sodium cyanide produces 1-methylpyrrole-2-acetonitrile.

iv. The product is then acylated at the free α-position of te pyrole ring by 4-methylbenzoylchloride in the presence o aluminum chloride to give 1-methyl-5-n-toluylpyrrol-2-acetonitrile.

v. The last further undergoes alkaline hydrolysis to finally produce tolmetin. [2]

Therapeutic Uses

Tolmetin is used for:

• Reducing pain, joint stiffness and swelling due to arthritis.
• Treatment of juvenile rheumatoid arthritis

Side Effects

Side effects of Tolmetin are:

• Nausea
• Vomiting
• Heartburn
• Diarrhea
• Upset stomach
• Dizziness
• Headache
• Hypertension
• Ringing in ears
• Mood changes
• Symptoms of heart failures
• Kidney problems
• Stiff neck
• Liver disease
• Allergic reactions

MCQs

Q.1 Choose the correct statements related with the physicochemical properties of drug Tolmetin.

I. Molecular weight = 147.0 gm/mol

II. It forms crystals from Acetonitrile

III. Melting point is 156 ^oC

 a) I, III

b) II, III

c) III

d) I, II

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

 a) i-C, ii-A, iii-B, iv-D

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

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

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

Q.3 Tolmetin inhibits

I. DNA polymerase enzyme

II. DNA dependent RNA polymerase enzyme

III. Prostaglandin synthetase enzyme

IV. Nucleosidases

a) I , II

b) III

c) III , IV

d) IV

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

• Tolmetin: Opioid Antagonist
• Asenapine: Benzodiazepine
• Clozapine: Benzazepine
• Haloperidol: buterophenone

a) TFFT

b) TTTT

c) TTFF

d) FFTT

Q.5 Find the INCORRECT statement amongst the following related with the SAR of Tolmetin?

I. Replacement of the 5-p-toluoyl group with p-chlorobenzoyl moiety have little changes on the activity of drug.

II. 4-methyl-5-p-chlorobenzoyl analog is 4 times more potent then tolmetin.

III. Substituting the chloro group with the p-methyl group blocks the oxidative metabolism which increases the duration of action by 1 day.

IV. Propionic acid analogue is more potent

Q.6 Number of chiral carbons present in the structure of tolmetin?

a) 0

b) 1

c) 2

d) 3 

Q.7 Side effect of drug Tolmetin include?

a) Symptoms of heart failure

b) Upset stomach

c) Kidney problems

d) All of the above

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ANSWERS

1-b

2-a

3-b

4-d

5-d

6-a

7-d

REFERENCES