Pentazocine opioid analgesics

IUPAC nomenclature

2-dimethylallyl-5,9-dimethyl-2′-hydroxybenzomorphan

Classification

• Pentazocine falls under category of opioid analgesics.

Physiochemical Properties

Mechanism of Action

Pentazocine antagonizes the opioid effects by competing at the receptor site. It mainly compete the opioid mu receptor site.

Structure Activity Relationship

SAR for morphine analogues can be summarized as follows:

• Replacement of phenolic hydroxyl into –OCH₃/-OC₂H₅ will make the compound less analgesic and cough suppression will also takes place.
• Replacement of alcoholic hydroxyl with –OCH₃ makes the compound 5 times more active.
• Replacement of alcoholic hydroxyl with -OC₂H₅  makes the compound 2.4 times more active than morphine.
• Replacement of alcoholic hydroxyl with –OCOCH₃ will also activates the compound by 4.2 times.
• Replacement of alcoholic hydroxyl with ketone group inactivates the compound and makes it lesser active.
• By hydrogenation of alicyclic unsaturated linkage, activity increases by 1.2 times.
• On replacement of the methyl group from tertiary nitrogen by hydrogen atom, activity decreases.
• On replacement of N-CH₃ by NCH₂CH₂Ph, activity increases by 14 times.
• When the methyl group of tertiary nitrogen replaced by N-allyl/methallyl/propyl, the compound so formed acts like the Morphine antagonist.
• When the methyl group of tertiary nitrogen replaced by N(CH₃)₂ Cl^– , compound have curare action and it do not possesses any analgesic activity.

Method of synthesis

i. 3,4-dimethylpyridine undergoes reaction with methyl iodide to produce 1,3,4-trimethylpyridinium iodide.

ii. The above formed compound is then reacted with 4-methoxybenzyl magnesium chloride to give 2-methoxybenzyl-3,4-dimethyl-1,2-dihydropyridine.

iii. Double bond of the last formed compound is hydrogenated using palladium catalyst to produce 3-methoxybenzyl-3,4-dimethyl-1,2,3,4-tetrahydropyridine.

iv. Intramolecular alkyation and simultaneous demethylation of the resulting compound leads to formation of 2-hydroxy-2,5,9-trimethylbenzo-6-morphane.

v. Above formed compound undergoes N-demethylation by cyanogens bromide to form 2-hydroxy-5,9-dimethylbenzo-6-morphane-N-normetazocine.

vi. On alkylation of the resulting product by 1-bromo-3-methyl-2-butene gives pentazocine.[1]

Therapeutic Uses

Pentazocine is used for:

• Relieve moderate to severe pain

Side Effects

Side effects Pentazocine are:

• Dizziness
• Drowsiness
• Constipation
• Tiredness
• Lightheadedness
• Stomach pain
• Rash
• Difficulty urinating
• Mood changes
• Stomach upset

MCQs

Q.1 Choose the correct option related with the mechanism of action of drug Pentazocine?

a) Acts as Opiate receptor antagonist

b) Mainly Competes with opioid sigma receptors

c) Mainly competes with opioid kappa receptors

d) All of the above

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

a) Treatment of diarrhea

b) As an anesthetic

c) Relieve moderate to severe pain

d) All of the above

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

I. Replacement of alcoholic hydroxyl with  -OC₂H₅  makes the compound 2.4 times more active than morphine.

II. Replacement of alcoholic hydroxyl with –OCOCH₃ will also activates the compound by 4.2 times.

III. Replacement of alcoholic hydroxyl with ketone group inactivates the compound and makes it lesser active.

IV. By hydrogenation of alicyclic unsaturated linkage, activity increases by 1.2 times

a) I, IV

b) II, III

c) III, IV

d) I, II, III, IV

Q.4 Number of chiral carbons present in the structure of Pentazocine is?

a) 0

b) 1

c) 2

d) 3

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

I. Molecular weight = 582 gm/mol

II. Melting point = 110.2^oC

III. White to very tan crystalline powder

IV. Ring structure absent

a) FFTF

b) TFFT

c) FTTF

d) TFFF

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

I. Pentazocine: 2-dimethylallyl-5,9-dimethyl-2′-hydroxybenzomorphan

II. Mechlorethamine: 2-Chloro-N-(2-chloroethyl)-N-methylethan-1-amine

III. Ifosfemide: N,3-Bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amide 2-oxide

IV. Carmustine: 1,3-Bis(2-chloroethyl)-1-nitrosourea

a) I, II

b) I, II, III, IV

c) II , III

d) III, IV 

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

 a) i-B, ii-D, iii-C, iv-A

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

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

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

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ANSWERS

1-a

2-c

3-d

4-b

5-a

6-b

7-d

REFERENCES