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The blood-brain barrierA protective filter of tightly packed cells that limits which substances can pass from the blood into the brain.Read more → matters because it decides which drugs can reach the brain at all. This is why some psychiatric treatments work while their close chemical relatives do not. It is a selective barrier formed by tightly sealed brain capillary cells, called tight junctions, wrapped by astrocyte end-feet (the supporting foot-like processes of astrocyte glial cells). For example, imagine two similar molecules, one lipophilic (fat-soluble) and one charged (electrically charged, water-soluble): only the lipophilic one crosses easily into the brain. In practice, this is exactly why levodopa (L-DOPA) treats Parkinson's disease while dopamine itself, given as a tablet, cannot.

Tight junctions between the endothelial (lining) cells of brain capillaries block substances that would normally leak through gaps in blood vessels elsewhere in the body. Astrocyte end-feet wrap around these capillaries and support this barrier function. Lipophilic and small uncharged molecules cross the blood-brain barrierA protective filter of tightly packed cells that limits which substances can pass from the blood into the brain.Read more → relatively easily, while charged or large molecules are largely excluded unless an active transporter carries them across. Circumventricular organs, small brain regions such as the area postrema, lack a full blood-brain barrier, letting them sense circulating hormones and toxins directly. Say a patient is given intravenous dopamine for low blood pressure: the dopamine cannot cross the barrier to treat their Parkinson's disease. In practice, oral levodopa, its lipophilic precursor, does cross, and drug design for brain conditions often modifies a molecule specifically to improve this crossing.

• Some drugs enter brain capillary cells easily yet still achieve low brain levels, because a pump returns them to the blood. Which transporter is chiefly responsible?
• Levodopa is water-soluble yet still reaches the brain in useful amounts. Which mechanism explains how it crosses the barrier despite its poor lipid solubility?
• Domperidone blocks dopamine receptors yet rarely causes movement side effects, unlike metoclopramide. Which property best explains this difference between the two drugs?
• Newer antihistamines cause far less drowsiness than older ones such as chlorphenamine. Which pair of properties best accounts for this reduced sedation?

• Levodopa, a lipophilic precursor that crosses the blood-brain barrierA protective filter of tightly packed cells that limits which substances can pass from the blood into the brain.Read more →, unlike dopamine itself which is charged and excluded.
• Tight junctions, seal brain capillaries against free diffusion, whereas capillaries elsewhere in the body are comparatively leaky.
• Circumventricular organs, lack a full blood-brain barrierA protective filter of tightly packed cells that limits which substances can pass from the blood into the brain.Read more →, unlike most of the brain, allowing direct hormone and toxin sensing.
• Lipophilic drugs, cross the barrier readily, rather than charged or large molecules which need an active transporter.

• That transporter recovers a neurotransmitterA chemical messenger that nerve cells release to signal to the next cell.Read more → at synapsesThe tiny gap between two nerve cells where a chemical signal passes from one to the other.Read more →, not at capillaries.
• That pump maintains ion gradients rather than expelling drugs.
• Tight junctions prevent free passage between these cells.
• Red cells are not a transport route across this barrier.
• The drug crosses effectively even with an entirely intact barrier.

• Localise the clue to the relevant anatomical level, cell type, pathway or molecular process.
• Map that structure or process to its normal function.
• Predict the deficit or clinical sign produced when it is disrupted.
• Reject options that belong to a neighbouring structure, pathway or level of explanation.