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

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

Naloxone

IUPAC nomenclature

(4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-(prop-2-en-1-yl)-2,3,4,4a,5,6-hexahydro-1H-4,12-methano[1]benzofurano[3,2-e]isoquinolin-7(7aH)-one.

Classification

  • Naloxone is an opioid antagonist.

 

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 327.4 g/mol
2 Physical appearance Crystals from ethyl acetate.
3 Melting point 200-205°C
4 Solubility Soluble in chloroform
5 Octanol/water partition coefficient 2.09
6 Presence of ring Piperidine, furane, cyclohexane, phenyl
7 Number of chiral centers 3

 

Mechanism of Action

Naloxone shows antagonistic effects by binding with the opioid receptors. It mainly binds with mu-opioid receptors, but can also binds with kappa and gama receptors.

 

Structure Activity Relationship

SAR for opiates can be summarized as follows:

  • Replacement of phenolic hydroxyl into –OCH3/-OC2H5 will make the drug 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 drug.
  • 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 Drug 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

Naloxone is synthesised by alkylation of 14-hydroxydihydronormorphinane by allylbromide.

 

Therapeutic Uses

Naloxone is used for:

  • Emergency treatment of known or suspected opioid overdose
  • In diagnosing an overdose of an opioid

 

 Side Effects

Side effects Naloxone are:

  • Body aches
  • Fever
  • Sweating
  • Runny nose
  • Watering eyes
  • Goose bumps
  • Weakness
  • Stomach cramps
  • Nervousness
  • Sneezing
  • Hypertension
  • Diarrhea
  • Nausea
  • Vomiting
  • Seizures in babies
  • Spasms

 

MCQs 

Q.1 Choose the correct statements related with the physicochemical properties of drug Naloxone.

I. Molecular weight = 230 gm/mol

II. It forms crystals from ethyl acetate

III. Melting point is 200-205 oC

 a) I, III

b) II

c) III

d) I, II

Q.2 Match the following of the drugs with their correct Brand names.

i. Naloxone A. Felbatol

 

ii. Felbamate B. Dilantin

 

iii. Phenytoin C. Narcan

 

iv. Clozapine D. Leponex

 

 a) i-C, ii-A, iii-B, iv-D

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

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

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

Q.3 Naloxone can bind with:

I. Mu-opioid receptors

II. Sigma-opioid receptors

III. Kappa-opioid receptors

IV. Gama opioid receptor

a) I , II, III, IV

b) I, III, IV

c) III , IV

d) IV

Q.4 Correct sequence for True/false for the classification of the drug can be?

  • Naloxone: Opioid Antagonist
  • Dolasetron: Antiemetic drug
  • Almotriptan: Hallucinogenic agent
  • Tegaserod: 5-HT3 receptor antagonist

a) TFFT

b) TTTT

c) TTFF

d) FFFF

Q.5 Find the INCORRECT statement amongst the following related with the SAR of Opiates?

a) On replacement of the methyl group from tertiary nitrogen by hydrogen atom, activity decreases.

b) On replacement of N-CH3 by NCH2CH2Ph, activity increases by 14 times.

c) When the methyl group of tertiary nitrogen replaced by N-allyl/methallyl/propyl, the compound so formed acts like the Drug Agonist.

d) 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

Q.6 Which drug is synthesized by alkylation of 14hydoxydihydronormorphinane by Allylbromide?

a) Naloxone

b) Tolmetin

c) Felbamate

d) Primidone

Q.7 Side effect of drug Naloxone include?

a) Goose bumps

b) Runny nose

c) Diarrhea

d) All of the above

 

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ANSWERS

1-c

2-a

3-b

4-c

5-c

6-a

7-d

 

REFERENCES

[1] Vardanyan R, Hruby V. Synthesis of essential drugs. Elsevier; 2006 Mar 10.

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