title: Characterization of novel selective H1-antihistamines for clinical evaluation in the treatment of insomnia.
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.
authors: Neurocrine Biosciences, 12780 El Camino Real, San Diego, California 92130, USA.
authors: Wilna J
authors: WJ
authors: Moree
authors: Bin-Feng
authors: BF
authors: Li
authors: Florence
authors: F
authors: Jovic
authors: Timothy
authors: T
authors: Coon
authors: Jinghua
authors: J
authors: Yu
authors: Raymond S
authors: RS
authors: Gross
authors: Fabio
authors: F
authors: Tucci
authors: Dragan
authors: D
authors: Marinkovic
authors: Said
authors: S
authors: Zamani-Kord
authors: Siobhan
authors: S
authors: Malany
authors: Margaret J
authors: MJ
authors: Bradbury
authors: Lisa M
authors: LM
authors: Hernandez
authors: Zhihong
authors: Z
authors: O'Brien
authors: Jianyun
authors: J
authors: Wen
authors: Hua
authors: H
authors: Wang
authors: Samuel R J
authors: SR
authors: Hoare
authors: Robert E
authors: RE
authors: Petroski
authors: Aida
authors: A
authors: Sacaan
authors: Ajay
authors: A
authors: Madan
authors: Paul D
authors: PD
authors: Crowe
authors: Graham
authors: G
authors: Beaton
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004115:Dimethindene / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004569:Electroencephalography / Q000187:drug effects; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006634:Histamine H1 Antagonists / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013379:Substrate Specificity
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D006634:Histamine H1 Antagonists; D011976:Receptors, Muscarinic; D004115:Dimethindene