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

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.

 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