Blood brain barrier: implication of drug metabolism in the penetration of methylhydroxycoumarin in rat.

Abstract

Abstract It is generally believed that apolar substances, by their lipotropic virtue, penetrate through biological membranes and distribute widely in the body, whereas polar substances have limited access to the central nervous tissue. Thus, the term blood brain barrier is designated to describe a lipid-containing membrane or barrier which limits the accessibility of polar substances to the brain. This concept holds well in most cases. In a few instances, however, fairly liposoluble substances such as morphine (1, 2) demonstrate a low distribution to the brain. On the other hand, we have observed that chlorpromazine sulfoxide, a polar substance, was found in the brain in a substantial amount following an intraperitoneal injection to rats, even after a rigorous perfusion of the brain with hypertonic as well as isotonic NaCl or KCl solutions (unpublished observations). These facts raised the question whether liposolubility per se is the sole factor determining the permeability of a drug through a blood brain barrier.