Morphine is an narcotic analgesic,a principal alkaloid obtained from Poppy plant,Papaver somniferum.

1. DEVELOPMENT OF MORPHINE
AGONISTS AND ANTAGONISTS
Presented by
Tejaswi.G
University College Of Technology
Osmania University

2. CONTENTS
 Introduction
 History
 Classification
 Structure of Morphine
 Mechanism of action
 Chemistry of Morphine
 Structure Activity Relationship
 Development of Morphine Analogues
o Agonist
o Antagonist
 Uses of Morphine
 Conclusion
 References

3. INTRODUCTION
• ANALGESIC- A drug that selectively relieves pain by
acting in the CNS or on peripheral mechanism without
significantly altering consciousness .
• OPIOID ANALGESICS are also known as narcotic
analgesics, that act on CNS, usually used for the
treatment of acute and chronic pain, for thousands of
years.
• OPIUM, a dark brown resinous material from unripe
seeds of Poppy.

4. HISTORY
• The writings of
Theophrastus around
200BC describe the use of
opium in medicine ;
however evidence suggests
that the opium is used in
Sumerian cultures early as
3500BC. The initial use of
opium was as a tonic, or it
was smoked.

5. • The pharmacist
Surterner first isolated
an alkaloid from
opium in 1803.He
named it as
MORPHINE, after
MORPHEUS, the
Greek God Of
Dreams.

6. • Codeine, Thebaine and papavareine are other medicinally
important alkaloids that were later isolated from latex of opium
poppy.
• Morphine was among the first compounds to undergo structure
modification.
• Ethyl morphine was introduced as a medicine in 1898.
• Diacetyl morphine(Heroin)which may be considered to be the
first synthetic prodrug, was synthesized in 1874 and marketed as
a non-addicting analgesic, anti-diarrheal and anti tussive agent
in 1898.

7. CLASSIFICATION OF OPIOIDS

8. MORPHINE
• Morphine is the principal
alkaloid in opium
and still widely used.
Therefore it is describe
as prototype.
Biological Source: It is obtained from the
juice or latex from the
unripe seed pods of
the Papaver somniferum.
Family : Papavaraceae

9. Structure Of Morphine
3D Structure2D Structure

10. MECHANISM OF ACTION
• As morphine binds to opioid receptors, molecular signalling activates the
receptors to mediate certain actions.
• There are three important classes of opioid receptors and these are:
• μ receptor or Mu receptors - There are three subtypes of this receptor,
the μ1, μ2 and μ3 receptors. Present in the brainstem and the thalamus,
activation of these receptors can result in pain relief, sedation and euphoria
as well as respiratory depression, constipation and physical dependence.
• κ receptor or kappa receptor - This receptor is present in the limbic
system, part of the forebrain called the diencephalon, the brain stem and
spinal cord. Activation of this receptor causes pain relief, sedation, loss of
breath and dependence.
• δ receptor or delta - This receptor is widely distributed in the brain
and also present in the spinal cord and digestive tract. Stimulation of this
receptor leads to analgesic as well as antidepressant effects but may also
cause respiratory depression.

13. Structure activity Relationship
Of Morphine

14. STRUCTURE

15. STRUCTURE

16. STRUCTURE

17. STRUCTURE

29. Agent class Example Action
Agonist
• Morphine
• fentanyl
• pethidine
activation of all receptor
subclasses, though, with
different affinities
Antagonist naloxone devoid of activity at all
receptor classes
Agonist-Antagonist nalorphine pentazocine agonist activity at one type
and antagonist activity at
another
Partial Agonist buprenorphine activity at one or more, but
not all receptor types
On the basis of these receptors, drugs can be
divided into four groups.
a. agonists
b. antagonists
c. agonist-antagonists
d. partial agonists

30. Morphine Sulfate
• Morphine sulfate is the analgesic used most often for
severe,acute,and chronic pain. It is available in
intramuscular,subcutaneous,oral,rectal and intrathecal dosage
forms.
• 3-6 times more potent when given intramuscularly than when
given orally.
• Half life -3hrs(intra muscular)

31. Codeine Phosphate
• It is weak µ agonist, methyl ether of morphine.
• Activity:20% that of Morphine
• Half Life: 3.5hrs
• Treats: moderate pain, cough, diarrhoea.
• Trade name:PANADOL

32. Hydromorphone Hydrochloride
• Activity: potent µ agonist,(8 times greater than morphine)
• Half life : 2.5hrs(Parenteral)
• 4hrs(oral)
• Trade Name: Dilaudid

33. Oxymorphone Hydrochloride
Activity: potent µ agonist,(10 times greater than morphine)
• Half life:3-4hrs
• Treats: moderate to severe pain
• Because of its 14-hydroxy group, has low antitussive activity.
• Trade Name: Numorphan

34. Oxycodone Hydrochloride
• Activity: it is about equipotent with morphine
• Half life: 4hrs
• Treats: Moderate to severe pain
• Trade Name: Oxycontin,Percodan

35. Meperidine Hydrochloride
• Activity:It is µ agonist having 1/10th of potency of Morphine
• Half life:3-4hrs
• Treats:extensively used in Obstrics,when given I.V respiratory
depression of newborn child is minimised.
• Trade name:Demerol

36. Fentanyl Citrate
• Activity:it is µ agonist and 80times greater potency than
morphine
• Treats:Fentanyl patch is used for chronic pain.Used in
combination with Nitrous oxide for balanced anaesthesia.
• Trade Name:DUROGESIC

37. Buprenorphine
Hydrochloride
• Activity:20-50 times more potent than
morphine,partial agonist at µ,k receptors, receptors but
antagonises at ð receptors.
• Treats: treatment of those addicted to opioids, such
as heroin and oxycodon, but it may also be used to treat pain.
• Trade Name:Suboxone

38. Pentazocine
• Activity:It is Weak antagonist (1/30th potency of naloxone),at
receptors and agonist at k receptors.
• Treats: used to relieve moderate to severe pain. It may also be
used before surgery or with a general anesthetic.
• Trade Name:Talwin

39. Naloxone
• Activity: it is a pure opioid antagonist.
• Treats:It is drug of choice for treating Opioid respiratory and
CVS depression
• Trade name:Narcan

40. Nalbuphine Hydrochloride
• Activity: It is an antagonist at receptors and an agonist at k
receptors.
• Treats: Morphine Poisoning, severe to moderate pain.
• Trade name: Nubain

46. Before Addiction After Addiction

47. CONCLUSION
 Finally we conclude that Morphine structure has phenanthrene nucleus.
 Removal of 3-OH group reduces analgesic activity.
 Acetylation of 3-OH and 6-OH group produces very potent lipophilic
compound.
 6-OH and 7,8 double bond is not required for the analgesic
activity,elimination enhances the activity.
 N-Methyl group substitution with larger alkyl groups reduces the
activity.Substitution with larger araalkyl group increases the activity.
 N-Methyl group replacement with alkyl,methyl cyclopropyl
group - antagonist activity.

48. REFERENCES
• An Introduction to Medicinal Chemistry –
• Graham L. Patrick, 4th Edition.
• Organic Chemistry Natural Products – O.P
Agarwal, Volume – 1.
• /www.drugbank.ca/
• https://en.wikipedia.org/wiki/Morphine