In order to understand the mode of action of local anesthetic agents, it is essential to understand the process of nerve conduction.

MECHANISM OF ACTION 1 - Acetylcholine Theory Acetylcholine is involved in nerve conduction. Acetylcholine is a neurotransmitter at the nerve synapses. However, there is no evidence that acetylcholine is involved in neural transmission along the body of neuron.

MECHANISM OF ACTION 2 - Calcium Displacement Theory Local anesthesia was produced by displacement of calcium from some membrane sites that controlled permeability to sodium. Studies have shown that variation in concentrations of calcium did not affect local anesthetic potency.

MECHANISM OF ACTION 3 - Surface Charge Theory Local anesthetic agents act by binding to nerve membrane; and changing the electrical potential at the membrane surface. Local anesthetic agents made electrical potential at the membrane surface more positive, thus reducing the excitability of nerve by increasing threshold potential.

MECHANISM OF ACTION 4 - Membrane Expansion Theory Local anesthetic molecules diffuse to hydrophobic regions of excitable membrane, expanding some critical regions in nerve membrane; and thus preventing an increase in permeability to sodium ions. This theory explains local anesthetic activity of benzocaine which does not exist in cationic form, yet exhibits potent topical anesthetic activity.

MECHANISM OF ACTION 5 - Specific Receptor Theory It is the most favored theory today. Local anesthetic agents act by binding to specific receptors on sodium channels in the nerve membrane.