Dopamine and antianxiety activity.
Clinical trials have indicated that buspirone (Buspar) is effective in the treatment of anxiety with efficacy and dosage comparable to diazepam. Until recently it has been thought that antianxiety drugs must alter benzodiazepine receptor binding in vitro. However, buspirone lacks any structural similarity to te benzodiazepines and does not interact with the benzodiazepine/gamma-aminobutyric acid (GABA) axis. Specifically, buspirone neither stimulates nor inhibits [3H]benzodiazepine binding, does not affect the influence o GABA or halide anions on benzodiazepine binding, and does not interfere with GABA binding or uptake. Behavioral testing has revealed that buspirone does not produce muscle weakness, does not control seizures, does not potentiate the impairment of psychophysiological function or lethality produced by administration of CNS depressants, does not produce sedation/hypnosis and does not appear to possess any abuse potential or liability for physical dependence. Thus, buspirone has been termed an anxioselective agent. Buspirone appears to only interact with the dopaminergic system with reasonable potency and exhibits properties of both a dopamine agonist and a dopamine antagonist. This suggests that dopamine is implicated in the etiology and expression of anxiety. A discussion of this implication is presented with a review of the clinical efficacy of nonbenzodiazepine drugs, especially dopamine agonists and dopamine antagonists, in the management of anxiety. In addition, neuropharmacological studies which have investigated the role of dopamine in animal models of anxiety are considered. Finally, the multiplicity of dopamine receptors and their regional localization in the brain are considered in the formulation of an hypothesis which features a role for the dopaminergic agents in the pharmacotherapy of anxiety.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D013329:Structure-Activity Relationship
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D004298:Dopamine