Local anesthetics SACCP ACU Purushotham KN BG Nagara Chemistry Pharma chemistry Medicinal Chemistry SAR QSAR

1. LOCAL ANESTHETICS
Presented by-
Purushotham KN
Assistant Professor
SACCP, ACU,
B.G Nagara
Ay-2020-21

2.  Local anesthetics are drugs which reversibly
prevent the generation & propagation of active
potentials in all excitable membranes including
nerve fibers by stabilizing the membranes.
 Local Anesthetics are used to abolish the sensation
of pain in a restricted area of the body and for minor
surgical operations, when loss of consciousness is
not desired.
Purushotham KN, SACCP, ACU.
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3.  The area determined by the site and the technique of administration of
anesthetic agents.
The main uses are as follows:
 Surface / Topical anesthetics
Local anesthesia is applied to Mucous Membrane.
Ex: Larynx, Damaged skin surface
 Infiltration anesthetics
Local anesthesia is injected subcutaneously to paralyze the sensory nerve
ending
Ex: an area to be incised, Tooth extraction.
 Nerve block anesthesia
Local anesthesia is injected close to the nerve trunk.
 Cavdal anesthesia
Local anesthetic into the caudal canal, the sacral portion of the spinal canal.
 Epidural anesthesia
Anesthesia that creates a band of numbness from your bellybutton to your upper
legs.
 Spinal anesthesia
Purushotham KN, SACCP, ACU.
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4. Chemical Classification
1. Esters
1. Amino alkyl esters of PABA
1. Procaine
2. Chloroprocaine
3. Tetracaine
4. Butacaine
2. Alkyl esters of amino benzoic acid
1. Orthocaine
2. Benzocaine
3. Butylamino benzoate
3. Esters of benzoic acid
1. Cocaine
2. Piperocaine
3. Hexylcaine
4. Piperocaine
Purushotham KN, SACCP, ACU.
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5. 2. Amides
1. Aminoacyl amides
1. Lidocaine
2. Prilocaine
3. Bupivacaine
4. Etidocaine
5. Mepivacaine
2. Amino alkyl amides
1. Cinchocaine / Dibucaine
Purushotham KN, SACCP, ACU.
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6. 3. Urethanes
1. Diperodon/Diperocaine
4. Aminoketones
1. Falicaine
2. Dyclonine
5. Aminoethers
1. Chlorobutanol
2. Eugenol
3. Dimethisoquin
6. Miscellaneous agents
1. Benzyl alcohol
2. Articaine
Purushotham KN, SACCP, ACU.
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7. SAR of Local Anesthetics
SAR of Local Anesthetics containing an ester
linkage
General structure of LA containing an ester linkage
Purushotham KN, SACCP, ACU.
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Aryl--C--x--Aminoalkyl side chain
Aromatic group Ester Linkage
Aminoalkyl group
O

8.  Aryl group
 An aryl radical attached directly to the carbonyl results
into a conjugation which in terms enhances local
anesthetic activity.
 The aryl substituents which increase the electron
density of the carbonyl oxygen & enhances activity.
Eg: alkoxy/ amino/ alkylamino at ortho or para
position.
Purushotham KN, SACCP, ACU.
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9.  Bridge ‘X’
 The X may be carbon, nitrogen, oxygen or sulphur.
 The nature of ‘X’ affects duration of action and
relative toxicity.
 Amino alkyl group
 The amino group is considered as the hydrophilic
part of the molecule. The activity decreases the
irritation property increases in following order.
Primary < secondary < Tertiary Amine
 The alkyl position only influence the lipid solubility.
Purushotham KN, SACCP, ACU.
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10. SAR of Local Anesthetics containing an amide linkage
Aryl group
The alkyl substitution at ortho/ para position, enhances the activity.
It provides steric hindrance to the hydrolysis of the amide linkage and
contributes to the lipid solubility of molecule
Substituent ‘X’
In general ‘X’ May be Carbon – Isogramine
Oxygen – Lidocaine
Nitrogen – Phenacaine
Amino alkyl group
The nature and its relative contribution to activity is same as in the
compounds containing an ester linkage.
Purushotham KN, SACCP, ACU.
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CH3
CH3
NH N
O
CH3
CH3
Aryl group Substituted 'X'
Amino alkylgroup
Lidocaine
Aryl---NH--C--Aminoalkylgroup
X
General Structure

11. Structures of Amide based LA
Lignocaine
IUPAC-
2-(diethylamino)-N-(2,6dimethylphenyl)acetamide
Purushotham KN, SACCP, ACU.
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CH3
NH
CH3
N
O
CH3
CH3

12. Etidocaine
IUPAC-
N-(2,6-dimethylphenyl)-2-[ethyl(propyl)amino]butanamide
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CH3
NH
CH3
N
O
CH3
CH3
CH3

13. Purushotham KN, SACCP, ACU.
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NH
CH3
NH
O
CH3
CH3
PRILOCAINE
IUPAC- N-(2-methylphenyl)-2-(propylamino)propanamide

14. MEPIVACAINE
IUPAC –
N-(2,6-dimethylphenyl)-1-methylpiperidine-2-carboxamide
Purushotham KN, SACCP, ACU.
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NH
CH3
O
CH3N
CH3

15.  Structures of Ester Based LA
Purushotham KN, SACCP, ACU.
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O
O
N CH3
CH3
NH2
O
O N
NH2
CH3
CH3
O
O
N CH3
O
N
O
CH3
O
CH3
O
Procaine Piperocaine
Butacaine Cocaine

16.  Reference
1. Wilson and Griswold
2. Burger
THANK YOU
Purushotham KN, SACCP, ACU.
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