Articles: anesthetics.
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Acta Pharmacol Toxicol (Copenh) · Nov 1977
Studies on the duration of local anaesthesia: structure/activity relationships in a series of homologous local anaesthetics.
When the number of carbon atoms on the piperidine-nitrogen of the mepivacaine molecule was increased up to four or five carbons, the toxicity of the compounds and the duration of their local anaesthetic effects were increased. With longer N-alkyl-chains, the general toxicity and the local anaesthetic potency - but not the tissue toxicity - were reduced. In dental infiltration anaesthesia only the short-chain compounds offered an acceptable local anaesthesia. In these tests, the medium-chain compounds had a very unfavourable quotient between dental anaesthesia and soft tissue anaesthesia, while the long-chain compounds could not be tested at all in man because of their tissue irritating properties.
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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.