title: TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) exhibits anxiolytic-like activity in a marble-burying assay in mice.
abstract: Numerous studies have suggested that the central alpha2-adrenergic receptor system may exert an important role in some types of human anxiety. The anxiolytic-like activity and potential side effect-like activities of the novel and purported alpha2-adrenergic compound TDIQ (5,6,7,8-1,3-dioxolo[4,5-g]isoquinoline) were compared to those of the anxiolytic drugs diazepam and buspirone, and the nonselective alpha2-adrenergic agent clonidine. Anxiolytic-like behavior was assessed in an object (marble)-burying assay, a selective test for the evaluation of known anxiolytics and identification of putative antianxiety compounds, that used mice housed either alone or in groups (5/cage). The rodents' antianxiety-like effect was defined as dose-related increases in the number of marbles that remained uncovered in their bedding material without concomitant disruption of their motor activities. Rotarod and inclined screen procedures were employed as potential indicators of side effects. An additional test monitored the heart rate (HR) and blood pressure (BP) of mice after the intravenous (IV) administration of doses of TDIQ. The reference compounds inhibited marble-burying behavior in a dose-related manner and produced various degrees of impairment in the side effect tests. TDIQ also inhibited object burying and displayed a wide separation between doses that produced anxiolytic-like activity and doses that produced some, if any, disruption of coordinated movement and/or motor activity. Moreover, the IV administration of TDIQ, up to 10 mg/kg, produced negligible effects on the HR and BP of mice. TDIQ could be a lead candidate for a new type of structural compound in the treatment of certain forms of anxiety.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298-0540, USA. ryoung@vcu.edu
authors.forename: Richard
authors.initials: R
authors.lastname: Young
authors.forename: Sandor
authors.initials: S
authors.lastname: Batkai
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Dukat
authors.forename: Richard A
authors.initials: RA
authors.lastname: Glennon
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: C451062:5,6,7,8-tetrahydro-1,3-dioxolo(4,5-g)isoquinoline; D014151:Anti-Anxiety Agents; D044005:Tetrahydroisoquinolines