Propylhexedrine

IUPAC nomenclature

(±)-1-cyclohexyl-N-methylpropan-2-amine.

Classification

Propylhexedrine  is an α-adrenergic agonist.

Physiochemical Properties

Mechanism of Action

I. Propylhexedrine causes serotonin, dopamine and norepinephrine transporters to reverse their direction of flow.

II. This leads to release of these transmitters from vesicles to the cytoplasm and then to the synapse.

III. Propylhederine also antagonizes the action of VMAT2 which results in more release of neurotransmitters.

Structure Activity Relationship

 The SAR of Adrenergic agonist can be discussed as follows:

• 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 methyl 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 substituent then it may act directly or indirectly. [1]

Method of synthesis

Propylhedrine can be synthesized from methamphetamine through reduction of the aromatic ring by Adam;s catalyst to form a cyclohexyl moiety.

Therapeutic Uses

Propylhexedrine is used:

• As a nasal decongestant

Side Effects

Side effects of propylhexedrine are:

• Restlessness
• Anxiousness
• Tremors
• Sweating
• Nasal rebound Congestion
• Nose dryness
• Burning nasal passage

MCQs

Q.1 Match the following with correct SAR of the drug Propylhexedrine.

 a) i-A, ii-D, iii-B, iv-C

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

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

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

Q.2 Correct sequence for the True/False for correct IUPAC names of the drug can be?

• Propylhexedrine: (±)-1-cyclohexyl-N-methylpropan-2-amine
• Metaraminol: (S,S)-2-methylamino-1-phenylpropan-1-ol.
• Pseudoephedrine: 4-(2-aminopropyl)phenol
• Hydroxyamphetamine: (RS)-[4-(1-Hydroxy-2-tert-butylamino-ethyl)-2-(4-methylbenzoyl)oxy-phenyl] 4-methylbenzoate

a) TFFF

b) FTTF

c) TFFT

d) FFFF

Q.3 Type of ring present in the structure of propylhexedrine?

a) Benzene

b) Imidazol

c) Cyclohexyle

d) Purine

Q.4 Propylhexedrine shows its effect through?

a) Agonism of α-receptors

b) Agonism of ß-receptors

c) Antagonism of α-receptors

d) Antagonism of ß-receptors

Q.5 Propylhexedrine is used for?

a) Treatment of AIDS.

b) Temporary relief of nasal congestion

c) As an antineoplastic drug

d) None of the above

Q.6 Which of the following drug and their classification are correct?

I. Pseudoephedrine is an α-adrenergic agonist.

II. Mechlorethamine is an alkylating agent.

a) I

b) II

c) I, II

d) None

Q.7 Propylhexedrine can be synthesized by reduction of?

a) Methamphetamine

b) Levorphanol

c) Clonazepam

d) Phenytoin

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ANSWERS

1-b

2-a

3-c

4-a

5-b

6-c

7-a

REFERENCES