Medicinal chemistry-I ,Narcotic agonists and antagonists - B.Pharmacy IV semester -Unit-V

1. NARCOTIC ANALGESICS AND NARCOTIC
ANTAGONISTS
BY
KENCHA SWATHI
ASSISTANT PROFESSOR
DEPT OF PHARMACEUTICAL CHEMISTRY
ADITYA BIPER
BANGALORE

2. NARCOTIC ANALGESICS
 The drugs interact with opioid receptors in the CNS. The
interactions result in the narcotic pharmacological effects of
analgesia, sedation and cough suppression are called as
narcotic analgesics.
Eg: Morphine sulphate
Codiene
Levorphanol
Diphenoxylate Hydrochloride
Pentazocine
Meperidine Hydrochloride
Loperamide Hydrochloride
Fentanyl citrate
Methadone Hydrochloride
Propoxyphene Hydrochloride
Anilerdine Hydrochloride

3. OPIOID RECEPTORS
 Opioid receptors are categorised into:
1.Delta opioid receptors(δ)
2.Kappa opioid receptors (k)
3.Mu opioid receptors (μ)
 All the three opioid receptors are located either in the
human brain or spinal cord tissues.
 Each receptor plays a major role in the control,regulation
and management of pain threshold.
 Orphan opioid receptor is the new one.

4. SAR OF MORPHINE ANALOGUES
 A ring and basic nitrogen are the most important structural features.
 A tertiary amine group is necessary for opioid activity with N-methyl
group displaying good agonistic properties.
 If the N atom contains higher alkyl groups then the compound shows
antagonistic activity.
Eg: Nalorphine & Naltrexone
 If OH group is changed to H group at 3rd position then activity will be
decreased 10 times.
 If OH group is changed to H group at 6th position then activity will be
increased.

5.  If the double bond between 7th and 8th position is reduced,then the
activity will be increased.
Eg: Oxycodone
 Replacement of OH group with ketone group at 6th position decreases
the narcotic agonistic activity.
Eg: Hydromorphone
Hydrocodone
 Methylation or acetylation of OH group at 3rd position ,activity will be
decreased.
Eg: Codeine
Heroin
 β –OH group at 14th position increases the narcotic agonistic activity.
 Acetylation of 6-OH group will increase the activity.
 Nitrogen containing a -CH₂ -CH₂ -phenyl group ,activity will increase by
10 folds.

6. MORPHINE SULPHATE
 Uses:1.Analgesic
2.In the treatment of long bone fractures,myocardial infarction.
3.To treat terminal stages of cancer,burn patients,post operative
patients,visceral pains.
4.To treat biliary colic and renal colic pain
5.Used as obstetric analgesia

7. CODEINE
 Uses: 1.Codeine is a cough reliever
2.To treat pain in irritable bowel syndrome.

8. MEPERIDINE HYDROCHLORIDE
 Uses: 1. Meperidine is commonly used in obstetrics
2.To treat post operative pain

9. ANILERDINE HYDROCHLORIDE
 Uses: 1.Narcotic agonist

10. DIPHENOXYLATE HYDROCHLORIDE
 Uses: 1.Narcotic agonist

11. LOPERAMIDE HYDROCHLORIDE
 Uses:1.To control acute & chronic diarrhoea.
2.To control idiopathic diarrhoea in AIDS

12. FENTANYL CITRATE
 Uses:1. Used for anaesthesia
2. Hypnotic
3. Local anaesthetic for spinal surgery.

13. METHADONE HYDROCHLORIDE
 Uses:1.Opioid analgesic
2. To control withdrawal symptoms from heroin & morphine

14. PROPOXYPHENE HYDROCHLORIDE
 Uses:1.Narcotic agonist

15. PENTAZOCINE
 Uses:1.Narcotic analgesic
2. To treat cardiac asthma.
3.To treat chronic pain

16. LEVORPHANOL TARTARATE
 Uses:1.Narcotic agonist
2.To treat severe pain

17. NARCOTIC ANTAGONISTS
 The drugs which are competitive antagonists that bind to the opioid
receptors with higher affinity than agonists but do not activate the
receptors.
 These drugs effectively blocks the receptor,preventing the body from
responding to opioids and endorphins.
Eg: Nalorphine hydrochloride
Levallorphan tartarate
Naloxone hydrochloride

18. NALORPHINE HYDROCHLORIDE
 Uses:1.Opioid antagonist
2.Antidote to reverse opioid overdose & drug dependance

19. LEVALORPHAN TARTARATE
 Uses:1.Opioid antagonist /antidote

20. NALOXONE HYDROCHLORIDE
 Uses:1.Narcotic antagonist
2.Used to treat respiratory depressant effects of opioid overdoses

21. SYNTHESIS OF FENTANYL CITRATE

22. SYNTHESIS OF METHADONE