This document discusses the biological source, isolation, and chemical structure of morphine. It was first isolated from the opium poppy Papaver somniferum in 1804. Morphine has a pentacyclic ring structure and is insoluble in water and some organic solvents. It exerts its effects by interacting with opioid receptors in the central nervous system. The document also discusses morphine metabolism and the importance of various functional groups like hydroxyl groups for receptor binding and activity. Finally, it describes approaches to modify the morphine structure by adding or removing rings to synthesize compounds with analgesic activity.

1. Presented by:
Mr. Afroj Shaikh
M.Pharm MNP

2.  Biological source: Dried latex extruded from
the seedpod of Papaver somniferum
(Papaveraceae)
 First active principle isolated from plant.
 Segnin 1804.
 Geographical source:- Mediterranean region
 Cultivation.
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3. Powdered opium
(shake with CaCl2 & Filter)
Add 10% NaOH solution
Filtrate
(Mor. Cod. Narceine) CHCl3
Precipitate
CHCl3 layer
Codeine
Aqueous layer
Acidify then Slightly alkaline NH4
Aqueous Sol.
Precipitate
Narceine
Morphine
Thebeine
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4. D(-) Morphine
B C Ring fusion is Cis
C D fusion is Trans
Chiral centre
Pentacyclic ring structure A,B,C,D,E.
OH functional group C3 C6
C4 C5 ether linkage – epoxy
C7 C8 unsaturation
tertiary amine function more basic.
Insoluble in Water, Chloroform, ether.
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5.  Limited Oral bioavailability
 Lipophilic but less
 Half life- 2-3 hrs.
 Elimination:- urine by glucuronide.
 Metabolism 3 and 6 O glucuronidation & O
methylation to Codeine.
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6.  Morphine exerts its major effects by interacting
with opioid receptors in the CNS
 Opioids activate 7- transmembrane GPCRs
located pre-synaptically and post-synaptically
along pain transmission pathways
 It has agonistic action at the μ, k and δ
 μ receptor:- Respiratory depression & analgesia
 k receptor:- Sedation
 δ receptor:- urinary retention and constipation
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7.  Based upon
 Phenolic OH group C3
&6 hydroxy
 7-8 unsaturation
 N methyl group
 Ether linkage
 Aromatic ring
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8.  Essential for the binding at Kappa or mu
receptor
 Changing to H or O CH3 decreases the activity
OH Morphine
H Activity deceases
O CH3 Codeine
Activity decreases
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9. > 5 C (In chain or ring ) Agonist
3-5 C with = /
Small cyclic / Aromatic
ring
Antagonist
Naloxone/Naltrexone
Aryl alkyl Increases 10 fold
 Interact hydrophobically with mu receptor
 Size of substitution on N determines the
potency and activity (Agonistic or
Antagonistic)
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10. Removal of OH reduces activity
Removal decreases
activity
Oxidation, acetylation, reduction 7=8 Increases activity
N-CH2=CH2-Ph increases
activity
N-CH2-CH2=CH2 creates
Antagonists
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11. Morphine
Codeine Heroin
Thebaine
C.R. Alder wright 1874
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12. Oxymorphone
Hydrocodone
Oxycodone
Hydromorphone 12

13.  Additional approach
 Addition of the extra ring in the morphine structure
gives active compound
 Simplification approach
 Deletion of the ring from morphine structure gives
active compound.
 Simplification approach is used for synthesis of a
new classes of compounds.
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14.  Addition of extra ring
in Morphine gives
Oripavines,
Naltrindole etc.
 Potency is comparable
to morphine but not
used clinically
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15.  Removing ring D
 Morphinans
 Useful analgesic
activity
 Oxygen bridge not
essential
 Eg. Dextrallorphan
 It acts as a σ1 receptor
agonist
 It has no significant
affinity for σ2, mu
opioid, or δ- opioid
receptor or serotonin
or NE.
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16.  Removing ring C & D from morphine nucleus
 Benzomorphans / Benzazocine
 It retains analgesic activity
 Eg:- Alazocine, Anazocine, Ketazocine,
Metazocine etc.
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17.  Removing ring B, C & D from morphine
nucleus.
 4- Phenyl pepiridine/Mepiridine series.
 It was discovered by chance in 1940 when
chemists were studying analogues of cocaine
for anti spasmodic activity.
 Eg:-Mepiridine, Bemidone,Properidine etc.
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18.  Removing ring B, C, D & E from morphine
nucleus. Methadone series.
 Retention Tertiary amine and aromatic function
It is an opioid used to
treat pain & as
maintenance therapy or to
help with detoxification in
people with opioid
dependence.
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