Which property explains rapid CNS entry by crossing the blood-brain barrier?

Which property explains rapid CNS entry by crossing the blood-brain barrier?

• A. Lipophilicity
• B. High molecular weight
• C. Hydrophilicity
• D. Positive charge at physiological pH

Answer: (D)

Lipophilicity is the main factor that allows rapid entry into the CNS across the blood-brain barrier. The BBB is a lipid-rich membrane, so drugs that are lipophilic can dissolve in and diffuse through the endothelial cell membranes more easily, moving passively into the brain down their concentration gradient. If a molecule is hydrophilic or ionized, it partitions poorly into the lipid membranes, slowing or preventing crossing. Higher molecular weight and a positive charge at physiological pH further reduce permeability because they decrease lipophilicity and hinder diffusion. So, lipophilicity best explains rapid CNS entry, while being positively charged at physiological pH would actually impede it.

Lipophilicity is the main factor that allows rapid entry into the CNS across the blood-brain barrier. The BBB is a lipid-rich membrane, so drugs that are lipophilic can dissolve in and diffuse through the endothelial cell membranes more easily, moving passively into the brain down their concentration gradient. If a molecule is hydrophilic or ionized, it partitions poorly into the lipid membranes, slowing or preventing crossing. Higher molecular weight and a positive charge at physiological pH further reduce permeability because they decrease lipophilicity and hinder diffusion. So, lipophilicity best explains rapid CNS entry, while being positively charged at physiological pH would actually impede it.