Abstract
Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-d-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and alpha(1)-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / pharmacokinetics
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Analgesics / pharmacology
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Animals
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / pharmacokinetics
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Benzimidazoles / pharmacology
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Brain / metabolism
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Calcium / metabolism
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Carrageenan
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Cell Line
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Dogs
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Female
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Humans
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Hyperalgesia / blood
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Hyperalgesia / chemically induced
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Hyperalgesia / drug therapy
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In Vitro Techniques
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Male
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Patch-Clamp Techniques
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
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Receptors, N-Methyl-D-Aspartate / physiology
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Structure-Activity Relationship
Substances
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Analgesics
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Benzimidazoles
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NR2B NMDA receptor
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Receptors, N-Methyl-D-Aspartate
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Carrageenan
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Calcium