Abstract
Polycyclic cage scaffolds have been successfully used in the development of numerous lead compounds demonstrating activity in the central nervous system (CNS). Several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and stroke, as well as drug abuse, can be modulated with polycyclic cage derivatives. These cage moieties, including adamantane and pentacycloundecane derivatives, improve the pharmacokinetic and pharmacodynamic properties of conjugated parent drugs and serve as an important scaffold in the design of therapeutically active agents for the treatment of neurological disorders. In this Minireview, we focus on the recent developments in the field of polycyclic cage compounds, as well as the relationship between the lipophilic character of these cage-derived drugs and the ability of such compounds to target and reach the CNS and improve the pharmacodynamic properties of compounds conjugated to it.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
MeSH terms
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Animals
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Brain / drug effects
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Brain / metabolism
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Brain / physiopathology
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Calcium Channels, L-Type / metabolism
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Cycloparaffins* / chemical synthesis
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Cycloparaffins* / therapeutic use
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Dopamine / metabolism
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Drug Design
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Humans
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Mice
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Monoamine Oxidase / metabolism
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Monoamine Oxidase Inhibitors / chemical synthesis
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Monoamine Oxidase Inhibitors / therapeutic use*
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Neurodegenerative Diseases / drug therapy*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / physiopathology
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Neuroprotective Agents / chemical synthesis
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Neuroprotective Agents / therapeutic use*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism
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Receptors, sigma / antagonists & inhibitors
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Receptors, sigma / metabolism
Substances
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Calcium Channels, L-Type
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Cycloparaffins
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Monoamine Oxidase Inhibitors
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Neuroprotective Agents
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Receptors, N-Methyl-D-Aspartate
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Receptors, sigma
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Nitric Oxide Synthase
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Monoamine Oxidase
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Dopamine