blood–brain barrier
The brain is a VIP club with a strict door policy. The blood–brain barrier is that velvet rope: a selective wall of tightly joined cells lining the brain's tiny blood vessels that decides which substances in the blood are allowed into brain tissue and which are turned away.
Its key feature is that the cells of brain capillaries are sealed together by tight junctions, leaving almost no gaps for drugs to slip through between cells. To enter, a drug must pass directly through cell membranes — favouring small, fat-soluble, uncharged molecules — or hitch a ride on specific transporters. The barrier is reinforced by efflux pumps like P-glycoprotein that actively eject many drugs back into the blood.
This barrier is a double-edged sword. It protects the brain from toxins but also blocks many useful drugs, such as most antibiotics and chemotherapy agents, from treating central nervous system disease. Inflammation, infection (such as meningitis) or tumours can break the barrier down, sometimes letting more drug in — occasionally exploited therapeutically.
Loratadine is designed to be poorly brain-penetrant, so it relieves allergy without much sedation, whereas older antihistamines like diphenhydramine cross the barrier and cause drowsiness.
Brain penetration is engineered in or out depending on the target.
Some brain regions (like the area postrema, the vomiting centre's chemoreceptor trigger zone) lack a full barrier — which is why some blood-borne signals and drugs can act there directly.