- Nalorphine is a mixed opioid agonist-antagonist.
|S. NO.||PHYSICAL AND CHEMICAL PROPERTIES|
|1||Molecular weight||311.4 g/mol|
|2||Physical appearance||Crystals from diethyl ether|
|4||Solubility||Slightly soluble in water; sparingly soluble in ether|
|5||Octanol/water partition coefficient||1.86|
|6||Presence of ring||Piperidine, cyclohexene, tetrahydrofuran, phenyl|
|7||Number of chiral centers||5|
Mechanism of Action
Nalorphine acts on to opioid receptors:
i. On mu-receptors it shows antagonistic effects
ii. On kappa receptors, it shows high-efficacy agonistic effects.
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 activate 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
i. Heroin is processed with cyanogens bromide to give N-cyano derivative.
ii. The N-cyano derivative is hen hydrolyzed by a solution of hydrochloric acid to transform into N-demethylated morphine which is also called as normorphine.
iii. The secondary amine group of normorphine undergoes alkylation with allylbromide to give the desired nalorphine.
Nalorphine is used for:
- To reverse the opioid overdose
- Challenge test to determine opioid dependence
Side effects Nalorphine are:
Q.1 What can be the correct IUPAC nomenclature of Nalorphine?
Q.2 Which amongst the following statements is/are incorrect related to the SAR of opiates?
I. On replacement of the methyl group from tertiary nitrogen by hydrogen atom, activity increases.
II. On replacement of N-CH3 by NCH2CH2Ph, activity decreases by 14 times.
III. When the methyl group of tertiary nitrogen replaced by N-allyl/methallyl/propyl, the compound so formed acts like the Drug antagonist
a) I, II
b) I, II, III
Q.3 Nalorphine can be synthesized from alkylation of ___________ by allylbromide?
Q.4 Side effects of drug Nalorphine is/are?
d) All of the above
Q.5 Match the following drugs with their correct molecular weight.
|i. Nalorphine||A. 311.4 gm/mol|
|ii. Phenacemide||B. 184.49 gm/mol|
|iii. Loxapine||C. 178.19 gm/mol|
|iv. Enflurane||D. 327.8 gm/mol|
a) i-A, ii-D, iii-C, iv-B
b) i-B, ii-A, iii-D, iv-C
c) i-A, ii-C, iii-D, iv-B
d) i-D, ii-C, iii-A, iv-B
Q.6 An example of drug from class Mixed-opioid antagonist is?
Q.7 The type of ring system found in the structure of Nalorphine is?
d) All of the above