title: A novel potent non-benzodiazepine anxioselective agent with reduced dependence liability: ICI 198, 256.
abstract: ICI 198,256, a member of the cinnoline series, was shown to be a potent anxiolytic agent in several species of animals. In addition, ICI 198,256 exhibited potent activity as an antagonist of both metrazole and bicuculline-induced convulsions. The salient features of ICI 198,256 are that it possesses minimal sedative liability, lower ethanol interaction and possibly lower dependence liability than benzodiazepines (e.g., diazepam). Neurochemically, this structurally novel anxiolytic compound is potent and selective for the Type 1 (cerebellar) BZ receptors in vivo as well as ex vivo, and in addition shows an agonist BZ-like profile in a variety of systems. Thus, ICI 198,256 may offer several significant advantages in the treatment of anxiety in humans than existing benzodiazepines.
authors.affiliation: Biomedical Research Department, ICI Pharmaceuticals, Wilmington, Delaware.
authors.forename: J B
authors.initials: JB
authors.lastname: Patel
authors.forename: B A
authors.initials: BA
authors.lastname: Meiners
authors.forename: A I
authors.initials: AI
authors.lastname: Salama
authors.forename: J B
authors.initials: JB
authors.lastname: Malick
authors.forename: J F
authors.initials: JF
authors.lastname: Resch
authors.forename: D C
authors.initials: DC
authors.lastname: U'Prichard
authors.forename: R E
authors.initials: RE
authors.lastname: Giles
authors.forename: B
authors.initials: B
authors.lastname: Hesp
authors.forename: M E
authors.initials: ME
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003521:Cyclopropanes / Q000009:adverse effects / Q000494:pharmacology*; D010793:Phthalazines / Q000009:adverse effects / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000517:prevention & control
chemical_list: D014151:Anti-Anxiety Agents; D003521:Cyclopropanes; D010793:Phthalazines; C067555:ICI 198256