Which part of the local anesthetic’s chemical structure determines if it is an ester or an amide?

The classification of local anesthetics into esters and amides is based on the structure of the intermediate chain within their chemical framework. In this context, the intermediate chain is the segment that connects the aromatic ring to the terminal amine. If this intermediate chain contains an ester linkage (–COO–), the local anesthetic is categorized as an ester. Conversely, if it contains an amide linkage (–CONH–), the anesthetic is designated as an amide. This structural characteristic is fundamental, as it influences not only the chemical properties of the anesthetic but also its metabolism and duration of action in the body.

The other parts of the anesthetic structure have different roles; for instance, the aromatic ring contributes to lipid solubility and the terminal amine is involved in the molecule's behavioral properties such as pH and ionization status, but it is the intermediate chain that ultimately differentiates between the ester and amide classes.