Solifenacin

IUPAC nomenclature

(3R)-1-Azabicyclo[2 2 2]oct-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

Classification

Solifenacin is an acetylcholine antagonist. It is a muscarinic antagonist.

Physiochemical Properties

Mechanism of Action

Solifenacin functions as antagonist for muscarinic receptors M3, M1 and M2 receptors. Antagonism of M3 receptors prevents the contraction of the detrusor muscles and antagonism of the M2 receptors prevents the contraction of smooth muscle in bladder. [1]

Structure Activity Relationship

• Either R₁ or R₂ must be heterocyclic or carbocyclic.
• The R₃ group can be hydrogen, hydroxyl, hydroxymethyl or amide.
• Most potent derivatives has X as an ester.
• X can also be either oxygen or absent completely.
• The N substituent can be quaternary ammonium salt or tertiary amine or both with different alkyl groups.
• Maximum potency obtained when the distance between the ring substituted carbons is 2 carbon units.

Method of synthesis

i. 1,2,3,4-tetrahydro-1-phenylisoquinoline reacts with ethyl chloroformate to give ethyl 3,4-dihydro-1-phenylisoquinoline-2(1H)-carboxylate.

ii. The latter compound on reacting with quiniclidin-3-ol, in presence of sodium hydride produces Solifenacin. [2]

Therapeutic Uses

Solifenacin is used for:

• Treatment of overactive bladder
• Reducing the frequent trips to bathroom
• Reducing the urge for frequent voids
• Reducing the leakage of urine

Side Effects

Side effects of Solifenacin are:

• Constipation
• Headache
• Dry mouth
• Blurred vision
• Dry eyes
• Tiredness
• Weakness

MCQ

Q.1 Subtypes of Muscarinic receptors antagonize by soilifenacin are?

a) M1, M2, M3

b) M2, M4, M5

c) M1, M2

d) M4, M5

Q.2 Therapeutic use of drug Solifenacin is/are?

a) Treatment of Alzheimer’s disease

b) Treatment of overactive bladder

c) Treatment of cancer

d) All of the above

Q.3 Which amongst the following are the correct statements with respect to the SAR of drug Solifenacin?

I. Either R₁ or R₂ must be heterocyclic or carbocyclic.

II. The R₃ group can be hydrogen, hydroxyl, hydroxymethyl or amide.

III. Most potent derivatives has X as an ester.

IV. ‘X’ can also be either oxygen or absent completely.

a) I, IV

b) I, II, IV

c) I, II, III, IV

d) II, III, IV

Q.4 Type of ring structures present in the structure of solifenacin?

a) Quiniclidine

b) Quinoline

c) Benzene

d) All of the above

Q.5 Correct sequence for the True/False for the physiochemical properties of the drug solifenacin?

I. Molecular weight is 363.5 gm/mol

II. Present in solid form

III. Melting point is between 134-136°C

IV. Soluble in organic solvents

a) TFTF

b) TTTT

c) FFFF

d)FFFT

Q.6 Correct statements for the IUPAC nomenclatures of the are?

I. Solifenacin: (3R)-1-Azabicyclo[2 2 2]oct-3-yl (1S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

II. Zaleplon: N-(3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide

III. Alprazolam: 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one

IV. Diazepam: 8-Chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a] [1,4]benzodiazepine

a) II, IV

b) I, II

c) I, III, IV

d) I, II, III, IV 

Q.7 Match the following drugs with their correct classifications-

 a) i-C, ii-A, iii-B, iv-D

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

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

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

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 Online Test for GPAT, Pharmacist,Drug Inspector

ANSWERS

1-a

2-b

3-c

4-d

5-b

6-b

7-a

REFERENCES