Norepinephrine

IUPAC nomenclature

(R)-4-(2-amino-1-hydroxyethyl)benzene-1,2-diol.

Classification

Norepinephrine is a nonselective adrenergic agonist. [1]

Physiochemical Properties

Mechanism of Action

• Norepinephrine acts on alpha-adrenergic receptors and functions as peripheral vasoconstrictor.
• It also acts on the beta-adrenergic receptors and functions as inotropic stimulator of the heart, and dilator of the coronary arteries.

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 methl 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 sunstituent then it may act directly or indirectly.[2]

Method of synthesis

i. Catechol reacts with chloroacetic acid and POCl₃ to give 4-chloroacetylcatechol.

ii. Norepinephrine is then obtained from 4-chloroacetylcatechol.

Therapeutic Uses

The drug used for the treatment of:

• Low blood pressure
• Used during CPR

Side Effects

Some of the common side effects of norepinephrine are pain, burning, irritation, discoloration of skin, headaches, blurred visions, trouble breathing, no or little urination, blue nails and lips, uneven heart rate, numbness, weakness and cold feeling.

MCQs

Q.1 What can be the correct IUPAC nomenclature of Norepinephrine?

a) (R)-4-(1-Hydroxy-2-(methylamino)ethyl)benzene-1,2-diol

b) (R)-4-(2-amino-1-hydroxyethyl)benzene-1,2-diol

c) (R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol

d) (R)-4-(2-amino-1-phenyl)benzene-1,2-diol

Q.2 Which amongst the following statements is/are incorrect related to the SAR of Norepinephrine?

I. Primary or secondary aliphatic amine separated by two carbons from a substituted benzene ring is essential for the high agonist activity

II. The hydroxyl substituted carbon must be in the L configuration for the maximal direct activity

III. When R1 is increased in size, activity of alpha receptors increases and activity of the beta receptors decreases.

IV. Activity of both alpha and beta receptors is minimum when R1 is methyl group.

a) I, II, III & IV

b) II, III & IV

c) II & IV

d) II & III

Q.3 Norepinephrine-

a) Acts on α-adrenergic receptors and functions as peripheral vaasoconstrictor

b) Acts on α-adrenergic receptors and functions as inotropic stimulator of the heart, and dilator of the coronary arteries.

c) Acts on ß-adrenergic receptors and functions as peripheral vasoconstrictor.

d) Both a) and b)

Q.4 The drug Norepinephrine is mainly used for?

a) Low blood pressure

b) High blood pressure

c) Myelomas

d) Prostate cancer

Q.5 Match the drugs with the correct classification.

 a) i-C, ii-D, iii-B, iv-A

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

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

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

Q.6 How many statements below are correct with respect to the side effects of the drug norepinephirine?

• Discoloration of skin
• Headaches
• Blurred visions
• Trouble breathing

a) 1

b) 2

c) 3

d) 4

Q.7 The type of ring system found in norepinephrine?

a) Benzene

b) Naphthalene

c) Oxazophosphorine

d) No ring present

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

ANSWERS

1-b

2-d

3-a

4-a

5-c

6-d

7-a

REFERENCES