Which Substance does not cross the blood-brain barrier?

Substances cross the blood-brain barrier (BBB) by a variety of mechanisms. These include transmembrane diffusion, saturable transpoers, adsorptive endocytosis, and the extracellular pathways. ... Most drugs in clinical use to date are small, lipid soluble molecules that cross the BBB by transmembrane diffusion Ref: guyton and hall textbook of medical physiology 12 edition page number: 671,672,673