What form of a molecule is typically referred to as unionized?

The term "unionized" refers to a form of a molecule that does not carry any net electrical charge. In the context of local anesthetics, the unionized or neutral form of the molecule is significant because it is the form that can more readily cross lipid membranes, such as neuronal cell membranes. This ability to diffuse through membranes is crucial for the onset of action of local anesthetics.

While charged forms of molecules (positively charged or negatively charged) are often more soluble in aqueous environments, they struggle to permeate lipid barriers, making the unionized, neutral form essential for the drug’s efficacy. The protonated form usually refers to a state where a molecule has accepted a proton (H+), resulting typically in a positively charged species, and thus is not considered unionized. The concept of pH and pKa is also pertinent in understanding the equilibrium between ionized and unionized forms, reinforcing the importance of the neutral molecule in local anesthetic action.