Abstract
Analogues of the known H(1)-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition.
MeSH terms
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Animals
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Brain / metabolism
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Dimethindene / metabolism
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Dimethindene / pharmacokinetics
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Dimethindene / pharmacology
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Dimethindene / therapeutic use
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Electroencephalography / drug effects
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Histamine H1 Antagonists / metabolism
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Histamine H1 Antagonists / pharmacokinetics
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Histamine H1 Antagonists / pharmacology*
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Histamine H1 Antagonists / therapeutic use*
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Humans
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Rats
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Receptors, Muscarinic / metabolism
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Sleep / drug effects
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Sleep Initiation and Maintenance Disorders / drug therapy*
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Substrate Specificity
Substances
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Ether-A-Go-Go Potassium Channels
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Histamine H1 Antagonists
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Receptors, Muscarinic
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Dimethindene