Central nervous system

The central nervous system (CNS) represents a special challenge for pharmacological therapy. Unlike most other anatomical regions, the CNS is particularly well isolated from foreign substances. The blood-brain barrier uses specialized tight junctions to prevent passive diffusion of most drugs from the systemic circulation to the cerebral circulation. Therefore, drugs intended to act in the CNS must be small enough and hydrophobic to easily cross biological membranes, or they must utilize transport proteins existing in the blood-brain barrier to penetrate central structures.

Source: The central nervous system of the human (the brain and the spinal cord) at the Natural History Museum in London, England. Emőke Dénes

Hydrophilic drugs that fail to bind to facilitated or active transport proteins in the blood-brain barrier are unable to penetrate the CNS. It is possible to cross the blood-brain barrier using an intrathecal infusion of the drug, in which it is directly released into the cerebrospinal fluid (CSF). Although this approach can be used in the treatment of infectious or carcinomatous meningitis, the intrathecal route is not practical for drugs that need to be regularly administered to the patient.

References:

Brodal, Per. The central nervous system: structure and function. oxford university Press, 2004.

Rubinstein, Lucien Jules. Tumors of the central nervous system. Vol. 6. Armed Forces Institute of Pathology; sold by American Registry of Pathology, 1972.

Myers, Martin G., and David P. Olson. “Central nervous system control of metabolism.” Nature 491, no. 7424 (2012): 357-363.

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