title: TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo [4,5-g]isoquinoline): discovery, pharmacological effects, and therapeutic potential.
abstract: Chemically, TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) can be viewed as a conformationally restricted phenylalkylamine that is related in structure to amphetamine but does not stimulate (or depress) locomotor activity in rodents. In radioligand binding studies TDIQ displays selective affinity for alpha(2)-adrenergic receptor subsites (i.e., alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenergic receptors), and behavioral data suggest that it might exert an agonist (or partial agonist) effect at alpha(2)-adrenergic receptors or interact at alpha(2)-adrenergic heteroreceptors. Drug discrimination studies in rats indicate that TDIQ: (1) serves as a discriminative stimulus, (2) may be useful in the treatment of symptoms associated with the abuse of cocaine, and (3) exhibits a low potential for abuse. In addition, TDIQ exhibits a dose-dependent and wide dissociation between doses that produce an anxiolytic-like effect or an inhibition of "snack" consumption in mice and doses that produce minimal, if any, effects in tests that measure a potential for disruption of coordinated movement or motor activity. Also, TDIQ displays negligible effects on the heart rate (HR) and blood pressure (BP) of mice. Taken together, the preclinical data suggest that TDIQ exhibits a favorable ratio of therapeutic-like effects (anxiolytic, therapeutic adjunct in the treatment of cocaine abuse, and appetite suppression) to side effect-like activities (behavioral impairment, drug abuse, or adverse cardiovascular effect). As such, TDIQ could: (1) be a forerunner for a new type of chemical entity in the treatment of certain forms of anxiety and/or obesity and (2) serve as a structural template in the discovery and development of additional agents that might be selective for alpha(2)-adrenergic receptors.
authors: Department of Medicinal Chemistry, Box 540, School of Pharmacy, 410 North 12th Street, Virginia Commonwealth University, Richmond, Virginia 23298-6540, USA. ryoung@vcu.edu
authors: Richard
authors: R
authors: Young
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D009765:Obesity / Q000188:drug therapy; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C451062:5,6,7,8-tetrahydro-1,3-dioxolo(4,5-g)isoquinoline; D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D044005:Tetrahydroisoquinolines