Which property most readily increases a drug's ability to penetrate the brain?

• A. High lipophilicity
• B. High molecular weight
• C. High polarity
• D. Strongly bound to plasma proteins

Answer: (A)

Penetration into the brain is governed by the blood-brain barrier, which favors diffusion of compounds that can partition into and pass through lipid membranes. The most influential property for this is high lipophilicity, because it increases the drug’s ability to dissolve in and traverse the lipid bilayer of cerebral capillaries, enabling passive diffusion into brain tissue. In contrast, high molecular weight and high polarity reduce diffusion across the barrier, and strong plasma protein binding lowers the fraction of drug available to cross. So, among the options, high lipophilicity best enhances brain penetration.