Bloodbrain Barrier

Not all substances in the bloodstream can readily gain entry into the brain. This apparent barrier to drugs and other chemicals is relative rather than absolute, and in fact there are several barriers to substances entering the brain from the systemic circulation. The term blood-brain barrier is usually applied to the lack of passage of certain drugs or other exogenously administered chemicals into the brain.

One important property that determines entry to the brain from the systemic circulation is molecular weight. Compounds with molecular weights of about 60,000 and above tend to remain within the circulatory system. Furthermore, the portion of an administered drug that is bound to plasma proteins is unavailable for distribution to the brain (as well as to other tissues and organs), in part because of the high molecular weight of the plasma protein-drug complex.

There are two physicochemical factors particularly important in allowing a drug to enter the CNS. First, for compounds that are mainly un-ionized at plasma pH (pKa 7.4 or higher), the drug's solubility in lipids is an important determinant. A lipid-soluble agent can more easily penetrate lipid membranes, such as those found in the CNS. The proportion of drug that is un-ionized is another important determinant. These two properties cannot be completely separated, since un-ionized drugs are generally more lipid soluble than ionized ones.

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