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The Distribution of Drugs in the Central Nervous Sytem

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Transport Phenomena in the Nervous System

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 69))

Abstract

The relative exclusion of many drugs from the central nervous system (CNS) is generally attributed to the blood-brain and blood- cerebrospinal fluid (CSF) barriers. In the past, this phenomenon was more or less interpreted as an impedance to the entry of drugs into the CNS. However, it is now apparent that numerous factors regulate the entry, as well as the distribution and final concentration of drugs within the CNS22. For instance, the rate of penetration from blood into the CNS is not only dependent on the plasma concentration, the physical-chemical properties7, 26, and the degree of binding of the drug to plasma proteins15, 47, but also on cerebral blood flow and the general permeability of cerebral blood vessels8, 20.Other factors beside the rate of penetration which affect the distribution of drugs within the CNS include regional vascularity, cerebral blood flow5, 36, the rate of diffusion through the interstitial spaces30 and CSF, uptake and metabolism within neuronal and glial elements, and the rate of efflux or diffusion from brain to CSF10 or to blood28, as well as efflux from CSF to blood29. The role and significance of factors which affect the penetration of molecules into the CNS will be dealt with in detail in the chapter by Dr. Oldendorf and will be alluded to by us only where necessary. The purpose of this chapter is to present the results of a series of studies conducted in our laboratories, as well as those of others, which lend support to the concept that the CSF plays an important role in the distribution and regulation of drugs within the CNS.

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Authors and Affiliations

  1. Departments of Pharmacology, Medicine, and Neurology, Harvard Medical School, Boston, Massachusetts, USA

    A. V. Lorenzo & Reynold Spector

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  1. A. V. Lorenzo
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  2. Reynold Spector
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Editors and Affiliations

  1. National Research Council, Rome, Italy

    Giulio Levi

  2. University of Padua Medical School, Padua, Italy

    Leontino Battistin

  3. Research Institute of Neurochemistry, New York, New York, USA

    Abel Lajtha

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© 1976 Plenum Press, New York

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Lorenzo, A.V., Spector, R. (1976). The Distribution of Drugs in the Central Nervous Sytem. In: Levi, G., Battistin, L., Lajtha, A. (eds) Transport Phenomena in the Nervous System. Advances in Experimental Medicine and Biology, vol 69. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-3264-0_33

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  • DOI: https://doi.org/10.1007/978-1-4684-3264-0_33

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