JAMA : the journal of the American Medical Association
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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. ⋯ 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.