CODEINE
CODEINE
IUPAC nomenclature
7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol.
Classification
• Narcotic analgesics, Antitussives, Anti-diarrhoea
Physiochemical Properties
Mechanism of Action
• Codeine phosphate reduces intestinal motility through both a local and possibly
central mechanism of action. Codeine and its salt are absorbed from the gastro-
intestinal tract and onset of analgesic action occurs 30 to 45 minutes after
administration, when given orally
Structure Activity Relationship
SAR for Opiates can be summarized as follows:
• Replacement of phenolic hydroxyl into –OCH3/-OC2H5 will
make the drug less analgesic
• 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.
• 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 possess any analgesic activity.
Method of synthesis
Codeine is synthesized by methylation of the 3-hydroxy group of the morphine ring by
trimethylphenylammonium ethoxide.
Side Effects
• Respiratory depression, Circulatory depression, Respiratory arrest
• Cardiac arrest, Drowsiness, Nausea, Vomiting, Sweating
• Shortness of breath, Sedation, Dizziness, Constipation