Biomedical
Characteristics of compounds that cross the blood-brain barrier
Abstract
The article "Characteristics of compounds that cross the blood-brain barrier" discusses the mechanisms by which substances traverse the blood-brain barrier (BBB), focusing on transmembrane diffusion and transporters. It highlights that transmembrane diffusion is non-saturable and depends on the physicochemical properties of the substance. Additionally, the article notes that brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow can significantly alter the amount of a substance crossing the BBB. Transport systems can increase uptake of ligands by approximately tenfold and are influenced by physiological events and disease states. The article also mentions that most drugs in clinical use are small, lipid-soluble molecules that cross the BBB via transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes, for which transporters have been described in recent years.
Key Questions about Compounds Crossing the Blood-Brain Barrier
1. What are the primary mechanisms by which substances cross the blood-brain barrier?
The article identifies several mechanisms:
- Transmembrane Diffusion: This non-saturable process depends on the physicochemical characteristics of the substance.
- Transporters: Saturable transport systems can increase the uptake of ligands by approximately tenfold and are influenced by physiological events and disease states.
- Adsorptive Endocytosis: This mechanism involves the uptake of substances through receptor-mediated processes.
- Extracellular Pathways: These pathways involve the movement of substances through the extracellular matrix.
2. How do brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow affect the amount of a substance crossing the BBB?
These factors can significantly alter the amount of a substance crossing the BBB by influencing its permeability and transport mechanisms. For example, efflux systems can pump substances back into the bloodstream, reducing their concentration in the brain. Enzymatic activity can metabolize substances before they reach the brain, and plasma protein binding can limit the free concentration of substances available to cross the BBB. Cerebral blood flow can affect the delivery of substances to the brain tissue.
3. What types of substances are most likely to cross the blood-brain barrier?
Most drugs in clinical use are small, lipid-soluble molecules that cross the BBB via transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes, for which transporters have been described in recent years.
