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

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

Phentolamine

IUPAC nomenclature

3-[(4,5-Dihydro-1H-imidazol-2-ylmethyl)(4-methylphenyl)amino]phenol.

 

Classification

Phentolamine is nonselective α-adrenergic antagonist. It can also be categorize as an antidote.

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 281.35  g/mol
2 Physical appearance Present in crystalline solid form
3 Melting point 174.5°C
4 Solubility 4.59 mg/L in water
5 Octanol/water partition coefficient 3.3
6 Presence of ring Benzene and imidazoline rings are present
7 Number of chiral centers Not present

 

Mechanism of Action

i.  Phentolamine competitively blocks α-adrenergic receptors.

ii. It leads to relaxation of muscles and widening of blood vessels.

iii. Widening of blood vessels results in decrease in blood pressure.

Phentolamine also stimulates ß-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart which results in increase in the cardiac output. [1]

Structure Activity Relationship

  • Molecules with 2,6-disubstitutions, which assume an orientation where the phenyl and imidazoline rings are in different plans are having the a highest activity.
  • Electronic effects have only influence on the actions at H2; action on α-receptors are not influenced.
  • Substitutions at 3, 4 or 5 positions of the phenyl ring preclude potent activity at H2-receptor sites while the α-receptor activity is maintained. [2]

Method of synthesis

m-(p-toluidino)phenol is refluxed with 2-chloromethylimidazoline to give phentolamine.

Therapeutic Uses

Phentolamine is used for:

  • Reversing numbness after dental procedures
  • For the prevention of the events of high blood pressure
  • Treatment of accidental injection of certain drugs under the skin
  • Diagnosis of pheochromocytoma

 Side Effects

Side effects of Phentolamine are:

  • Pain at injection site
  • Change in heart rate
  • Headache
  • Weakness
  • Diarrhea
  • Redness and warmth in skin
  • Vomiting
  • Nausea
  • Dizziness

  

 MCQs

 Q.1 What can be the correct IUPAC nomenclature of  Phentolamine

a) 3-[(4,5-Dihydro-1H-imidazol-2-ylmethyl)(4-methylphenyl)amino]phenol

b) 3-[(1R,2S)-2-amino-1-hydroxypropyl]phenol

c) 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole

d) (RS)-4-(2-{[4-(4-hydroxyphenyl)butan-2-yl]amino}ethyl)benzene-1,2-diol

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

I. Molecules with 2,6-disubstitutions, which assume an orientation where the phenyl and imidazoline rings are in different plans are having the a highest activity.

II. Electronic effects have only influence on the actions at H2; action on α-receptors are not influenced.

III. Substitutions at 3, 4 or 5 positions of the phenyl ring preclude potent activity at H2-receptor sites while the ↑-receptor activity is maintained.

a) I, II

b) I, II, III

c) II, III

d) I

Q.3 m-(p-toluidino)phenol is refluxed with 2-chloromethylimidazoline to give?

a) Dobutamine

b) Sildosin

c) Phentolamine

d) Mthacholine

Q.4 Side effects of drug phentolamine is/are?

a) change in heart rate

b) Headache

c) Dizziness

d) All of the above

Q.5 Match the following drugs with their correct melting points-

i. Phentolamine A. 184-186°C
ii. Dobutamine B. 174.5°C
iii. Metaraminol C. 257°C
iv. Naphazoline D. 107.5°C

 a) i-D, ii-B, iii-A, iv-C

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

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

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

Q.6 An example of drug from class nonselective α-adrenergic antagonist?

a) Metaraminol

b) Dopamine

c) Albuterol

d) Phentolamine

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

a) Imidazoline

b) Ergorine

c) Cyclopropane

d) None of the above 

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ANSWERS

1-a

2-b

3-c

4-d

5-d

6-d

7-a

 REFERENCES

[1] Gould LA, Zahir MO, Ettinger ST. Phentolamine and cardiovascular performance. British heart journal. 1969 Mar;31(2):154.

[2] Malta E, Ong JS, Raper C, Tawa PE, Vaughan GN. Structure-activity relationships of clonidine-and tolazoline-like compounds at histamine and alpha-adrenoceptor sites. British journal of pharmacology. 1980 Aug;69(4):679.

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