Lipid soluble drugs cross the blood-brain barrier more easily than water soluble drugs. The penetration of acid and basic drugs depends on the lipid solubility of the unionised molecules.
If a drug is highly polar then it does not easily cross the blood-brain barrier. This is because highly polar drugs have lower concentrations of unionised molecules. For example amphetamine (base) penetrates more easily than adrenaline (acid) as it has less polar groups.
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