Toward understanding how the lactone moiety of discodermolide affects activity

Local anesthetics (LAs) are drugs that induce a temporary loss of sensation in a limited body area, preventing pain. Cocaine was the first local anesthetic discovered in the late 19th century. Cocaine is a benzoic acid ester obtained from the leaves of coca shrubs and was often used for its psychotropic effects. Cocaine was first isolated in 1860 by Albert Niemann. Sigmund Freud studied the physiological actions of cocaine. Carl Koller later introduced it into clinical practice in 1884 as a...

Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...

The extended Debye-Hückel equation indicates that the activity coefficient of an ion in an aqueous solution at 25°C depends on three partially interdependent properties: the ionic strength of the solution, the charge of the ion, and the ion size. 
The activity coefficient value for an ion is close to one when the solution has almost zero ionic strength, i.e., when the solution shows close to ideal behavior. As the ionic strength of the solution increases from 0 to 0.1 mol/L, a decrease in the...