Principles of Neuropharmacology and Experimental Therapeutics

**3**

**Chapter 1**

**Abstract**

**1. Introduction**

compartments [1].

transport [1, 2].

toxic materials out of the CNS [4].

Principles of

*Andrew H. Rodgers*

**Keywords:** blood-brain barrier (BBB)

Neuropharmacodynamics: As

The blood-brain barrier (BBB) is a highly selective semi-permeable membrane that separates the cerebral blood circulation from the brain and extracellular fluid in the central nervous system (CNS). The BBB is composed of endothelial cells, astrocyte end-feet and pericytes embedded in the capillary basement membrane. This system allows the passage of water, some gases and lipid-soluble molecules by passive diffusion, as well as, selective molecules such as glucose and amino acids. This review discusses pharmacodynamic concepts and methods that allow drugs to penetrate the BBB structure and enter the CNS and spinal nervous systems (SNS).

The blood-brain barrier (BBB) was discovered over 100 years ago by Paul Ehrlich during his studies on the brain [1]. Ehrlich's early observations that water soluble dyes stained all organs of animals except for their brains and components of the central nervous system (CNS) was the key to our present day understanding of the BBB system. Subsequently, other researchers observed that dyes injected into the blood stream did not enter the brain hence a barrier existed between the two

The BBB differs from normal membranes in that it possesses tight junctions between an endothelial cell/astrocyte wall with no pores to allow for transport unless materials are lipophilic, water, and/or an actively transported. The BBB is also lipophilic, free of aqueous electrolytes and highly electrical resistant. However, the BBB compartment can be traversed by lipophilic substances through passive diffusion, while other molecules that are substrates for transferases cross by direct

The BBB prevents most systemic therapies from penetrating the brain; however,

when cancer cells do penetrate the BBB from a peripheral origin, they generate neo-vascularization or cancer associated "vascular mimicry" structures (new blood vessels associated with tumor-generated penetrate breaks in the BBB) which can connect intracranial metastatic cancer cell colonies with the cerebral blood circulation [3]. If undesirable or toxic materials pass through the BBB into the CNS, a protective mechanism—the P-glycoprotein (P-gP) transfer system will transport

Applied to Neuro-Oncology

## **Chapter 1**
