Abstract
Cocaine's toxicity can be mitigated by blocking its interaction with sigma-1 receptors. The involvement of sigma-2 receptors remains unclear. To investigate their potential role, we have designed compounds through a convergent synthesis utilizing a highly selective sigma-1 ligand and elements of a selective sigma-2 ligand. Among the synthesized compounds was produced a subnanomolar sigma-2 ligand with an 11-fold preference over sigma-1 receptors. These compounds may be useful in developing effective pharmacotherapies for cocaine toxicity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Anticonvulsants / chemical synthesis*
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Anticonvulsants / chemistry
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Anticonvulsants / pharmacology
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Brain / metabolism
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Cocaine / toxicity*
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Cocaine-Related Disorders / drug therapy
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In Vitro Techniques
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Ligands
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Mice
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Oxazoles / chemical synthesis*
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Oxazoles / chemistry
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Oxazoles / pharmacology
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / pharmacology
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Radioligand Assay
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Rats
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Receptors, sigma / antagonists & inhibitors
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Receptors, sigma / metabolism*
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Seizures / chemically induced
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Seizures / drug therapy
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Sigma-1 Receptor
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
Substances
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Anticonvulsants
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Ligands
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Oxazoles
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Piperazines
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Receptors, sigma
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Thiazoles
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sigma-2 receptor
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Cocaine