Classification
I. Morphine and its analogues
Morphine
Ethyl Morphine
Codeine
Heroin
Nalorphrine
SAR of Morphine
Morphine's structure is separated into three section. They
are
1.
Modification of Alicyclic ring
2. Modification of aromatic ring
3. Modification of tertiary nitrogen
Modification of Alicyclic ring
The alcoholic hydroxyl
group at
C-6 when methylated, oxidized, esterified or removed
- Analgesic activity and Toxicity, increased.
Saturation of double bond at C-7 position
- more potent compound.
Example, Dihydro morphine
Bridging of C-6 and C-14
through ethylene linkage (-CH2-CH2-) - potent derivatives.
Modification of Aromatic Ring
Aromatic phenyl ring is essential.
Modification or Substitution on
phenolic hydroxyl group
decreases activity.
Modification of tertiary nitrogen
It is necessary for good activity.
N-Methyl substitution have
good agonistic property. When increased
the size of substituents (3-5 carbons) have antagonistic property.
N-allyl and N-cyclo alkyl group leads to narcotic
antagonistic property.
Epoxide Bridge
Removal of 3,4 epoxide bridge results in
morphinans.
Uses
Used as analgesic (pain reliever) in chemotherapy.
Only small amount is preferred due to drug dependence.
Adverse Effects
Minor side effects
- Sedation, mental clouding, lethargy. Respiratory depression, blurring of
vision, urinary retention.
Acute morphine poisoning
Lethal dose is 250 mg.
Manifestations are
coma, flaccidity, shallow and occasional breathing, cyanosis, pinpoint pupil.
Pulmonary edema occurs at terminal stages.
Death is due to respiratory failure.
Treatment - Respiratory support;
Gastric lavage if needed.
Anti-dote -
Naloxone 0.4-0.8 mg i.v repeated
every 2-3 min till respiration picks up.
