Medicinal Chemistry

1. LOCAL
ANESTHETICS

2. Local anesthetic (LA) is a medication that causes absence of pain sensation.
In the context of surgery, a local anesthetic creates an absence of pain in a
specific location of the body without a loss of consciousness, as opposed to a
general anesthetic.

3. History
The anesthetic properties of coca leaves (Erythroxylon coca Lam) became known to
Europeans from the natives of Peru, who chewed the leaves for a general feeling of
well-being.
The active principle of the coca leaf, however, was not discovered until 1860 by
Niemann, who obtained a crystalline alkaloid from the leaves, to which he gave the
name cocaine, and who noted the anesthetic effect on the tongue.

5. MOA
All LAs are membrane-stabilizing drugs; they reversibly decrease the rate of
depolarization and repolarization of excitable membranes (like nociceptors).
LA drugs act mainly by inhibiting sodium influx through sodium-specific ion channels
in the neuronal cell membrane (voltage-gated sodium channels).
When the influx of sodium is interrupted, an action potential cannot arise and signal
conduction is inhibited. The receptor site is thought to be located at the cytoplasmic
(inner) portion of the sodium channel.
Local anesthetic drugs bind more readily to sodium channels in an activated state,
thus onset of neuronal blockade is faster in rapidly firing neurons.

6. Classification of Local anesthetics
1. Ester based:
• Natural
- Cocaine
• Synthetic
• Benzoic acid derivatives: Cyclomethicaine, Piperocaine
• p- benzoic acid derivatives: Benzocaine, Procaine, Butacaine, Tetracaine, Benoxinate
2. Amide based: Lignocaine, Mepivacaine, Prilocaine, Etidocaine, Dibucaine
3. Amino ether based: Pramoxine
4. Amino ketone based: Dyclonine
5. Alcohol based: Benzyl alcohol, Eugenol
6. Miscellaneous: Phenacaine