Which property of local anesthetics affects their potency?

Lipid solubility is the property of local anesthetics that significantly affects their potency. Local anesthetics work by diffusing across neuronal membranes to block nerve conduction, and this process is highly dependent on their ability to dissolve in lipid (fat) environments. The more lipid-soluble a local anesthetic is, the more effectively it can penetrate the nerve membrane and bind to sodium channels.

Higher lipid solubility not only increases the ability of the anesthetic to reach its target site within the nerve membrane but also often correlates with a longer duration of action and heightened potency. This is because lipid-soluble anesthetics tend to be more effective at higher concentrations within the nerve tissue, which enhances their numbing effect.

Other properties, such as hydrophilicity and molecular weight, may play roles in the overall pharmacokinetic and pharmacodynamic profile of local anesthetics, but they are not the primary determinants of potency. Vasodilation capability can influence the duration and onset of action by affecting the rate at which the anesthetic is removed from the site of action through the blood supply, but it does not directly correlate with potency in the same way that lipid solubility does.