Neural blockade by local anesthetics

R. H. de Jong

Local anesthetics block nerve impulse propagation by occluding transmembrane sodium channels, so preventing depolarization. First, the uncharged lipid-soluble anesthetic base pentrates the membrane; then the positively charged cation binds to anionic components of the sodium channel's internal axoplasmic mouth. Though primarily a carrier, the base contributes to blockade by causing the membrane to swell, so pinching the sodium channels. Dissolved in water, local anesthetic salt crystals dissociate into anesthetic cation and base-proportional to the drug's fixed pKa and the tissue's variable pH. The cation-base concentration ration is critical to optimal neural blockade. If there is too little base, few anesthetic molecules will penetrate to the neural target; if too little cation, few sodium channels will be plugged.