Brain capillary permeability coefficients

Levin, V.A. 1980. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23 682. 

Levin VA (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23 682-684 Link G, Athias P, Grynberg A, Pinson A, Hershko C (1989) Effect of iron loading on transmembrane potential, contraction, and automaticity of rat ventricular muscle cells in culture. J Lab Clin Med 113 103-111 Link G, Pinson A, Hershko C (1993) Iron loading of cultured cardiac myocytes modifies sarcolemmal structure and increases lysosomal fragility. J Lab Clin Med 121 127-134... 

The permeability coefficient, P (cm/s), is defined by the following operational equation for non-directed flux from the blood to the brain across the cerebral capillaries. It can be determined by measuring the concentration of a drug in the plasma and brain as a function of time [56, 59] ... 

Figure 15.33. In vivo log permeability coefficient of rat brain capillaries (log Rnn) as a function of log octanol/water partition coefficient (logPo/ ), the most commonly used measure of lipophilicity. For compounds in italic, the log distribution coefficient measured at physiological pH was used (logDp/ ). Values denoted with a star are for guinea pig. The strong deviants below the line that are denoted with diamonds are known substrates for P-glycoprotein, a multidrug transporter that actively removes them from the brain.

Capillaries in the Brain (the Blood-Brain Barrier). Capillaries in the brain are less permeable than capillaries in other tissues. This limited permeability, which is frequently called the blood-brain barrier, is essential for brain function. Reduced permeation provides a buffer that maintains a constant brain extracellular environment, even at times when blood chemistry is changing. The basis for this lower permeability is the relative paucity of pores in the brain endothelium. Therefore, molecules that move from blood to brain must diffuse through the endothelial cell membranes. As expected from this observation, the permeability of brain capillaries depends on the size and lipid solubility of the solute. In general, molecules that are larger than several hundred in molecular weight do not permeate into the brain. Empirical relationships between cerebrovascular permeability and the oil / water partition coefficient have been developed [26] (see Figure 5.27) ... 

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