FIVE ROUTES

Crossing needs the right permit

Some molecules diffuse through, some are carried by proteins, some ride vesicles, some are pushed back out, and some are blocked at the gap.

Each route has its own rules, so each drug has its own fate.

PASSIVE

Small and oily gets through

Small Molecules lighter than roughly 400 to 500 daltons cross much more easily

Lipid-soluble Fat-loving molecules dissolve through the cell membrane

Few hydrogen bonds Molecules that cling to water tend to stay in the blood

Oxygen, carbon dioxide, and caffeine are examples of molecules that pass this way.

CARRIERS

Transporters bring in what the brain needs

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GLUT1

A glucose carrier that is very abundant in brain endothelial cells

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LAT1

Carries large neutral amino acids, and the Parkinson's drug levodopa rides on it

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Many more

Other carriers handle lactate, vitamins, nucleosides, and more

A drug that looks like a nutrient can borrow a nutrient's door.

RECEPTOR-MEDIATED

Vesicle shuttles for big cargo

Receptors such as the transferrin receptor and the insulin receptor bind their cargo. The cell wraps it in a vesicle, carries it across, and releases it on the brain side. This is called receptor-mediated transcytosis.

Drug designers use it by attaching a drug to an antibody or ligand that binds one of these receptors.

Turn a barrier route into a delivery route.

EFFLUX

Pumps that throw drugs back

Efflux pumps such as P-glycoprotein (P-gp) and BCRP sit on the blood-facing side of the endothelial cell. They push many drug molecules back into the blood even after the drug has entered the cell.

A drug can be small and oily and still fail because a pump ejects it.

UNIT 4 STUDY COMPLETE

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Ready for the Fab Challenge?

You've seen the five routes across the barrier and why a drug's properties decide which one it can use.