B.

PHARAMACY SEM – IV

MEDICINAL CHEMISTRY – I
(13PH0402)

Unit – 5 NARCOTIC AND

NON-NARCOTIC
ANALGESICS

Presented by - Ms.Chandni Padwani

Assistant professor,
Faculty of pharmacy,
Marwadi University, Rajkot
NARCOTIC AND NON-NARCOTIC ANALGESICS

1. MORPHINE AND RELATED DRUGS

2. SAR OF MORPHINE ANALOGUES

3. NARCOTIC ANTAGONISTS
 INTRODUCTION

 ANALGESIC - “A drug that selectively relieves pain by acting in the CNS or on

peripheral pain mechanisms, without significantly altering consciousness”.

 Analgesics relieve pain as a symptom, without affecting its cause. They are used when
the noxious stimulus (evoking the pain) cannot be removed or as adjuvants to more
etiological approach to pain.

Analgesics are divided into two groups, viz.

A. Opioid/narcotic/morphine-like analgesics.

B. Non-opioid/non-narcotic/aspirin-like/antipyretic or anti-inflammatory analgesics

 CLASSIFICATION

1. NARCOTIC AND NON-NARCOTIC ANALGESICS :

A. MORPHINE AND RELATED DRUGS :

i. Morphine sulphate

ii. Codeine

iii. Meperidine hydrochloride

iv. Anilerdine hydrochloride

v. Diphenoxylate hydrochloride

vi. Loperamide hydrochloride

vii. Fentanyl citrate*

viii. Methadone hydrochloride*

ix. Propoxyphene hydrochloride

x. Pentazocine

xi. Levorphanol tartarate

B. NARCOTIC ANTAGONISTS :

i. Nalorphine hydrochloride

ii. Levallorphan tartarate

iii. Naloxone hydrochloride

2. ANTI-INFLAMMATORY AGENTS :

i. Sodium salicylate

ii. Aspirin

iii. Mefenamic acid*

iv. Meclofenamate

v. Indomethacin

vi. Sulindac

vii. Tolmetin
viii. Zomepriac

ix. Diclofenac

x. Ketorolac

xi. Ibuprofen*

xii. Naproxen

xiii. Piroxicam

xiv. Phenacetin
viii. Acetaminophen

ix. Antipyrine

x. Phenylbutazone.
 SAR OF MORPHINE ANALOGUES

 The STRUCTURE – ACTIVITY relationship (SAR) is the relationship between the

chemical or 3D structure of a molecule and its biological activity.

 Enables the determination of the chemical groups responsible for evoking a target
biological effect in the organism.

 SAR is an advance design to find the relationships between chemical structure and
biological activity of studied compounds.

 Therefore it is the concept of linking chemical structure to a chemical property or

biological activity including toxicity.

 The theory of SARs is to produce new drugs with similar structure and effects as the
original one but with having more potency and improved side-effects.
 Moreover, SARs are essential for toxicological studies on a compound.

 SARs have been used since long ago to design chemicals with the commercially wanted
properties and thus they are important while designing drugs as the chemicals with desired
pharmacological and therapeutic activities are known.
 FACTORS CONSIDERED

 There are various factors that should be considered while developing the
mechanism of SARs, these are:

 The size and shape of the carbon skeleton,

 The nature and degree of substitution and
 The stereochemistry
 During modifications on a drug analogue,

 Effects on water solubility,

 Transport through membranes,

 Receptor binding,

 Metabolism and other pharmacokinetics properties should be considered.

 Computer assisted molecular modelling helps to solve this problem by

providing accurate targeting.
GENERAL STRUCTURE AND NUMBERING OF MORPHINE
ACTIVITIES OF OPIODS
A. PHENOLIC HYDROXYL GROUP (POSITION C3)
HYDROXYL AT 6TH POSITION (C6)
7,8 DOUBLE BOND
B. N-METHYL GROUP (POSITION C9)
OPIOD ANTAGONISTS
BETA H/OH MOEITY ON POSITION C14
CHAIN LENGTH AT C17
LOSS OF OTHER RINGS
SUMMARY
 LINKS FOR VIDEOS

https://youtu.be/WXnPighjXhI

https://youtu.be/Cy2sU381_dM

https://youtu.be/et0eTa7hnck
 MORPHINE AND RELATED DRUGS
1. MORPHINE SULPHATE

 MOLECULAR FORMULA – C₁₇H₁₉NO₃

 MECHANISM OF ACTION – Morphine

binding to opioid receptors blocks transmission
of nociceptive signals, signals pain-modulating
neurons in the spinal cord,.

 The net effect of morphine is the activation of

descending inhibitory pathways of the CNS
as well as inhibition of the nociceptive
(sensation of pain ) in afferent neurons of the
PNS, which leads to an overall reduction of the
nociceptive transmission.
 MEDICINAL USES OF MORPHINE

 Morphine is used to relieve moderate to severe pain.

 Morphine extended-release tablets and capsules are only used to relieve

severe (around-the-clock) pain that cannot be controlled by the use of other
pain medications.
 CODEINE

2. CODEIN

 MOLECULAR FORMULA – C18H21NO3

 MECHANISM OF ACTION – Codeine is an

opioid and an agonist of the mu opioid receptor
(MOR).

 It acts on the central nervous system to have an

analgesic effect.
 It is metabolised in the liver to produce morphine
which is ten times more potent against the mu
receptor.
 MEDICINAL USES OF CODEINE

 It is typically used to treat mild to moderate degrees of pain.

 Greater benefit may occur when combined with paracetamol (acetaminophen) or

a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

 Codeine is used to relieve coughing (ANTITUSSIVE).

 MEPERIDINE HYDROCHLORIDE

3. MEPERIDINE HYDROCHLORIDE
(PETHIDINE)

 MOLECULAR FORMULA –
C15H21NO2

 MECHANISM OF ACTION

 Like morphine, pethidine exerts its

analgesic effects by acting as
an agonist at the μ-opioid receptor.
MEDICINAL USES OF MEPERIDINE HYDROCHLORIDE

 Pethidine is the most widely used opioid in labour and delivery.

 Meperidine is an opioid medication used to treat moderate-to-severe pain.

 FENTANYL CITRATE*

4. FENTANYL CITRATE*

 MOLECULAR FORMULA –
C22H28N2O

 MECHANISM OF ACTION
 Biochemically, it is a Mu-selective opioid
agonist. However, it has the capability to
activate other opioid system receptors such as
the delta and potentially the kappa-receptors.
Consequently, the activation of these
receptors, particularly the Mu-receptors,
produces analgesia.
MEDICINAL USES OF FENTANYL CITRATE*

Fentanyl is an opioid medication used as part of anesthesia to help prevent

pain after surgery or other medical procedure.

Fentanyl is used to treat breakthrough pain (sudden episodes of pain that occur
despite round the clock treatment with pain medication) in cancer.

Who are tolerant (used to the effects of the medication) to narcotic pain
medications.
SYNTHESIS OF FENTANYL CITRATE*

(Phenyl ethyl chloride)

 ANILERDINE HYDROCHLORIDE

4. ANILERDINE HYDROCHLORIDE

 MOLECULAR FORMULA –
C₂₂H₃₀Cl₂N₂O₂

 MECHANISM OF ACTION Anileridine is

an opioid receptor agonist belonging to the
piperidine class with analgesic activity. By
binding to and activating opioid receptors in
the central nervous sytem (CNS),
anileridine mimics the endogenous opioids
resulting in a decrease of nociceptve
neurotransmitters and eventually an
analgesic effect.
MEDICINAL USES OF ANILERDINE HYDROCHLORIDE

 Anileridine is a synthetic opioid and strong analgesic medication.

 It is a narcotic pain reliever used to treat moderate to severe pain.

 Narcotic analgesics act in the central nervous system (CNS) to relieve pain.
5. DIPHENOXYLATE HYDROCHLORIDE

 MOLECULAR FORMULA – C30H32N2O2

 MECHANISM OF ACTION Like other opioids,

diphenoxylate acts by slowing intestinal
contractions, allowing the body to consolidate
intestinal contents and prolong transit time,
thus allowing the intestines to draw moisture
out of them at a normal or higher rate and
therefore stop the formation of loose and liquid
stools
MEDICINAL USES OF DIPHENOXYLATE HYDROCHLORIDE

 Diphenoxylate is used to treat diarrhea in adults.

 It is only available as a combination drug with a subtherapeutic dose of atropine to

prevent abuse.
6. LOPERAMIDE HYDROCHLORIDE

 MOLECULAR FORMULA – C29H33ClN2O2

 MECHANISM OF ACTION – It is an opioid-

receptor agonist and acts on the μ-opioid receptors in
the large intestine.

 It works like morphine, decreasing the activity of the

myenteric plexus, which decreases the tone of the
longitudinal and circular smooth muscles of the
intestinal wall.

 This increases the time material stays in the

intestine, allowing more water to be absorbed from
the fecal matter.
MEDICINAL USES OF LOPERAMIDE HYDROCHLORIDE

 It is a medication used to decrease the frequency of diarrhea.

 It is often used for this purpose in inflammatory bowel disease and short bowel
syndrome.

 It is not recommended for those with blood in the stool, mucus in the stool, or fevers.

 This includes control of

acute nonspecific diarrhea,

mild traveler's diarrhea,
irritable bowel syndrome,
chronic diarrhea due to bowel resection, and
chronic diarrhea secondary to inflammatory bowel disease.
7. METHADONE HYDROCHLORIDE

 MOLECULAR FORMULA –C21H27NO•HCl

 MECHANISM OF ACTION – Levomethadone is s

a μ-opioid receptor agonist

 Methadone has been shown to reduce neuropathic

pain in rat models, primarily through NMDA
receptor antagonism.
MEDICINAL USES OF METHADONE HYDROCHLORIDE

 Methadose Oral Tablets (methadone hydrochloride) are indicated for the:

 Management of moderate to severe pain when a continuous, around-the-

clock opioid analgesic is needed for an extended period of time.

 Detoxification treatment of opioid addiction (heroin or other morphine-like

drugs).

 Maintenance treatment of opioid addiction (heroin or other morphine-like

drugs), in conjunction with appropriate social and medical services.
SYNTHESIS OF METHADONE HYDROCHLORIDE

METHADONE
8. PROPOXYPHENE HYDROCHLORIDE

 MOLECULAR FORMULA –C21H27NO•HCl

 MECHANISM OF ACTION –

 Dextropropoxyphene acts as a mu-opioid

receptor agonist.

 It also acts as potent, noncompetitive nicotinic

acetylcholine receptor antagonist, as well as a
weak serotonin reuptake inhibitor.
MEDICINAL USES OF METHADONE HYDROCHLORIDE

 It is intended to treat mild pain and also has antitussive (cough

suppressant) and

local anaesthetic effects.

9. PENTAZOCIN

 MOLECULAR FORMULA – C19H27NO•HCl

 MECHANISM OF ACTION –

 It is believed to work by activating (Kappa)

κ-opioid receptors and μ-opioid receptors.

 It delivers its effects on pain by interacting with

the opioid receptors.
 MEDICINAL USES OF PENTAZOCIN

 Pentazocine injection is used to relieve moderate to severe pain.

 It may also be used before surgery or with a general anesthetic (medicine

that puts you to sleep).

 It acts on the central nervous system (CNS) to relieve pain.

10. LEVARPHANOL TARTARATE

 MOLECULAR FORMULA –
C17H23NO•C4H6O6•2H2O

 MECHANISM OF ACTION –

 Like other mu-agonist opioids it is

believed to act at receptors in the
periventricular and periaqueductal gray
matter in both the brain and spinal
cord to alter the transmission and
perception of pain.
 MEDICINAL USES OF LEVARPHANOL TARTARATE

 This medication is used to treat moderate to severe pain.

 Levorphanol is an opioid pain reliever.

As analgesic in preoperative medication where an opioid analgesic

is appropriate.

 It is up to 8 times more potent than morphine.

 NARCOTIC ANTAGONISTS

1. NALORPHINE HCL

 MOLECULAR FORMULA –
C19H21NO3.HCL

 MECHANISM OF ACTION –

 Nalorphine is a mixed opioid agonist–

antagonist. It acts at two opioid
receptors—at the mu receptor it has
antagonistic effects, and at the kappa
receptors it exerts high-efficacy
agonistic characteristics.
 MEDICINAL USES OF NALORPHINE

 This medication is used to Reverse effects of anrcotic oversdoses.

 Analgesic
2. LEVALLORPHANE
TARTARATE

 MOLECULAR FORMULA –
C19H25NO

 MECHANISM OF ACTION –

 Levallorphan antagonizes opioid

effects by competing for the
same receptor sites.
MEDICINAL USES OFLEVALLORPHAN TARTARATE

 Levallorphan was formerly widely used in general anesthesia, mainly to

reverse the respiratory depression produced by opioid analgesics.

Levallorphan was also used in combination with opioid analgesics to reduce

their side effects.
3. NALOXONE HYDROCHLORIDE

 MOLECULAR FORMULA – C19H21NO4 •

HCl

 MECHANISM OF ACTION –

 It antagonizes opioid effects by

competing for the mu, kappa, and sigma
opiate receptor sites in the CNS, with the
greatest affinity for the mu receptor.
 Naloxone Hydrochloride Injection is indicated for the complete or partial
reversal of opioid depression, including respiratory depression.

 Naloxone hydrochloride is also indicated for the diagnosis of suspected or

known acute opioid overdosage.