PMID: 9190855Jun 1, 1997Paper

The passage of azidodeoxythymidine into and within the central nervous system: does it follow the parent compound, thymidine?

The Journal of Pharmacology and Experimental Therapeutics
S A Thomas, M B Segal

Abstract

The transport of azidodeoxythymidine (AZT) into and within the central nervous system (CNS) has special clinical significance due to the ability of AZT to alleviate certain neurological symptoms associated with the acquired immunodeficiency syndrome (AIDS). AZT was thought to be similar to its parent compound, thymidine, in that it entered the CNS via the choroid plexuses (blood-CSF barrier) and could not cross the blood-brain barrier (BBB). However, a saturable transport system for thymidine at the BBB has recently been identified. The aim of this study was to test the hypothesis that AZT follows its physiological counterpart in its mode of entry into and movement within the CNS. Initial experiments using the in situ brain perfusion technique indicated that the blood-to-CNS transfer constants for [3H]AZT (blood-to-cerebrum; 0.95 +/- 0.12 microl/min/g) were significantly lower than those determined for [3H]thymidine. Also, [3H]AZT entered the CNS purely by a diffusive process. The movement of [3H]AZT within the CNS was further investigated by a ventriculocisternal perfusion technique and indicated that the majority of intraventricularly perfused [3H]AZT remained within the ventricles (79.9%), with little escaping to blood (14.1...Continue Reading

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