The blood–brain barrier: a wall with a pump
In most of the body, the tiny blood vessels are leaky — small molecules slip easily through gaps between the cells lining them. The brain is different. Its capillary cells are sealed together by tight junctions, with almost no gaps. This is the blood–brain barrier: a continuous wall that forces a drug to pass *through* cells, not between them. To cross, a drug essentially has to dissolve into the fatty cell membranes — so high lipophilicity and passive diffusion are the usual ticket in. Water-soluble drugs, large molecules, and most antibiotics are largely shut out.
But the barrier is not just a passive wall — it's an active bouncer. Even some lipophilic drugs that get in are caught by an efflux transporter called P-glycoprotein, which sits in the barrier cells and pumps the drug straight back into the blood. So a drug can be fat-soluble enough to enter, yet still fail to build up in the brain because P-glycoprotein keeps throwing it out.
The placenta: a barrier that mostly isn't
The placental barrier sounds reassuring, but the name is misleading. The placenta is built to *exchange* substances between mother and fetus, so it lets most drugs through. The same rule applies: lipophilic, small, un-ionized drugs cross readily by passive diffusion. Some efflux transporters, including P-glycoprotein, push a fraction back toward the mother, offering partial protection — but you should assume that a drug reaching the mother's blood can reach the fetus.