Abstract
The principle of direct administration of repeated doses of drugs either at or close to their site of action in the central nervous system is based on:
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the identification of specific receptors and neuro-active endogenous peptides which has considerably advanced our understanding of the functioning of the central nervous system. The notion of chemical transmission of information in specific pathways now underlies the early electrical model of Galvani.
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better understanding of the pharmacological action of endogenous and exogenous ligands, which was led to the development of specific and highly active drugs. Such drugs are now employed routinely in the treatment of chronic conditions such as intractable pain or spasticity. In the near future, it may also be possible to treat other neurological diseases by manipulation of the specific neuromediators or neuromodulators involved.
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the fact that high doses of drug are often required via the systemic route, giving rise to adverse reactions in other parts of the organism before the active agent reaches the target organ. Many drugs do not readily cross the blood-brain barrier, and are degraded in the periphery either in the digestive tract, liver or kidneys. This means that the therapeutic ratio is low for many drugs. Moreover, distribution in the central nervous system itself is not localized to the site of action (spinal cord for example) which can give rise to supra-spinal side effects.
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advances in technology which have stimulated development of implantable systems enabling local or regional administration of many drugs employed in endocrinology, oncology and neurology.
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Lazorthes, Y., Sallerin-Caute, B., Verdie, J.C., Bastide, R. (1991). Advances in Drug Delivery Systems and Applications in Neurosurgery. In: Symon, L., et al. Advances and Technical Standards in Neurosurgery. Advances and Technical Standards in Neurosurgery, vol 18. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6697-0_5
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