Opioid Analgesics - Narcotic Anlagesics - 0

http://www.gpatonline.
com
Pharmacology
CNS: Opioid Analgesics
Opioid Analgesics (Narcotic Anlagesics)

Analgsia : Unpleasant sensation evoked by external or internal noxious stimuli.
Analgesics: The drugs that relives the pain by acting in the CNS or on Pheripheral pain
mechanism.
It divide into Opioid analgesics and non-opioid (NSAIDs) analgesics.
Classification of Opiod analgesics present in papaver somniferum
1. Phenanthrene derivatives:
Morphine (10%), Codeine (0.5%), Thebaine (0.2%)
2. Benzisoquinoline derivatives:
Papavarine (1%), Noscapine (6%) (Narcotine)
Demethylation of Codeine to Morphine

Classification:
1. Narcotics agonist analgesics
A. Phenanthrenes:
Natural opium alkaloids: Morphine, Codeine
Semi-synthetic derivatives:
Morphine derivative: Hydroxymorphone, Oxymorphone
Codeine Derivatives: Hydrocodone, Oxycodone
B. Methadones: Methadone, Propoxyphene
C. Morphinan: Levorphenol
D. Phenyl piperidens (Meperidine): Pethidine, Fentanyl, Alfentanil, Sufentanil
2. Narcotic agonist-antagonist analgesics
A. Phenanthrenes Buprenorphine, Nalbuphine
B. Morphinan Butorphanol
C. Benzomorphan Phenazocine, Pentazocine
3. Narcotic antagonist:
Naloxone, Naltraxone
Tech Sanskar eLearning Solutions
http://www.gpatonline.com
Page 1 of 6
Pharmacology
Opioid Receptors:
Receptors
Endogenous
Substance
receptors
Endorphin
Agonist
Morphine
Partial
agonist
Buprenorphine
Nalorphine
Butorphanol
Naltrexone
Butorphanol
receptors
Dynorphin A, B
Nalorphine
---
Pentazocine
receptors
Enkephalins
Morphine
(Weak)
Antagonist
----
Naltrexone
Naloxone
Naltrexone (Weak)
Naloxone (Weak)
MOA of Opioids:
Fig. 1 Action of Opioid

Explanation of Fig. 1: Opioids excites neurons from periaqueductal gray matter (PAG) and
nucleus reticularis paragigantocellularis (NRPG). which project to retroventral medulla
which contain nucleus raphe magnus (NRM) 5-HT and enkephalin containing neurons
Page 2 of 6
Pharmacology
runs towards dorsal horn and exert an inhibitory influence on transmission (Substance P).
Opioids directly act on dorsal horn as well as peripheral terminal of nociceptive afferent
neurons.
Upon activations of opioids receptors ( and ) decreases c-AMP formation Opens K+
channels hyperpolarisation Decrease in release of Substance P (neurotransmitter)
On activation of receptors Suppresses N type Ca++ ion channels inhibition of Ca++
influx Hyperpolarisation.
SAR of Morphine:
Modification
Interpretation
Replacement of OCH3 at 3rd Position
Codeine decreased analgesic activity
Replacement of OC2H5 at 3rd Position
Ethylmorphine little analgesic activty
Replacement of -O-CO-CH3 at 3rd Position
Heroin increases analgesic but also
and 6th postion
increases addiction effect.
Dihydromorphinone or dihydrocodeine
14-Hydroxy dihydromorphine more potent
Oxidation at C-6
analgesics.
Page 3 of 6
Pharmacology
addition of OH at C-14
Bridging at C-6 and C-14
14 through ethylene
Etorphine 200 times more potent than
linkage
morphine
Modification at tertiary nitrogen (N-R)
Potent Antagonistic activity
Replacement of R with methyl, n-phenyl, nhexyl, allyl etcs.

Thenaine, Oripavine
Increased activity, selectivity, and decreased

toxicity.
Ethorphine
10000 time more potent than morphine but

no. of side effects, use as a sedative in
veterinary medicines.
SAR of Meperidine Class:
Removal of B,C, D rings
Morphine
Pethidine
Modification
4-phenyl
phenyl
group
Interpretation
with
hydrogen,
alkyl, Reduces Activity
aroalkyl or hetrocyclic group

Replacement of COOC2H5 by COC2H5
Prodine - increases analgesic activity
Replacement of N-CH3 by various aralkyl e.g.

group
Piminodine
Increased
analgesic
activity
Piperidine ring enlarge to 77 membered e.g. Proheptazine Active and potent

azepine ring
analgesic
Methadone Class:
Page 4 of 6
Pharmacology
Methadone series
Unlike mepridine series insertion of m-hydroxyl

m hydroxyl group in one of the phenyl ring of
methadone series causes a marked decreased in activity.
Methadone is more potent than isomethadone
Methadone
Isomethadone
Replacement of propionyl group (COC2H5) with hydrogen, hydroxyl, acetoloxy

decreases in activity.
Replacement of propionyl group (COC2H5) with amide group Racemoramide

(More active than methadone)
Racemoramide
Removal of any phenyl ring lead to decreases in activity.
Morphinanes
Does not process C4 C5

ether linkage.
N-Methyl
Methyl Morphinan (20% of activity)
Levo form possesses greater activity,

activity, Levorphenol shows 5% more potent than
morphine
Page 5 of 6
Pharmacology
dextro form of recemorphan is used as cough suppressant (Dextromorphan)
Benzomorphan series:
Compound
R1
R2
R3
R4
Benzomorphan
OH
CH3
Pentazocine
OH
CH2CH=C(CH3)2 CH3
CH3
Phenazocine
OH
CH2-CH2-C6H5
CH3
CH3
Metazocine
OH
CH3
CH3
CH3
Cyclazocine
OH
CH3
CH3
Trimethyl compounds is 3 time more potent than dimethyl amalogous
N-phenethyl
phenethyl derivatives possess 20 times greater potency than N-methyl
N methyl analogous.
Pentazocine and cyclazocine are classic antagonist. (Pentazocine - High analgesia less
addiction)
Narcotic antagonist:
Replacement of N-methyl
methyl group in morphine by larger alkyl group lowers activity and act as
antagonist.
antagonist activity increases in following order:
C2H5
<
C3H7
<
CH2CH=CH2
<
e.g. Nalorphine, Naloxone, Levallorphan
Page 6 of 6

Opioid Analgesics - Narcotic Anlagesics - 0

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Opioid Analgesics - Narcotic Anlagesics - 0

Uploaded by

Copyright:

Available Formats

http://www.gpatonline.

CNS: Opioid Analgesics