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.