Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder.
gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system (CNS). It exerts its rapid inhibitory action mostly through GABA(A) receptors, which are targets for benzodiazepines, barbiturates, neuroactive steroids and distinct anticonvulsive agents. There is considerable evidence that dysfunction of GABA(A) receptors or dysregulation of GABA concentrations in the CNS (or both) plays an important role in the pathophysiology of panic disorder. Currently, benzodiazepines are the only drugs directly targeting the GABA(A) receptors that are approved for the treatment of anxiety disorders. Because of their well-known anxiolytic effects, they are widely used in this setting, but side effects limit their use in long-term treatment. The question of whether drugs that selectively increase GABA concentrations in the CNS could improve symptoms of anxiety has been discussed. Recent investigations by our group have demonstrated that enhancement of endogenous GABA (through blockade of GABA transaminase by vigabatrin or through inhibition of GABA transporters by tiagabine) exerts anxiolytic effects on experimentally induced panic. Our studies in healthy volunteers have shown that both compounds lead to a significant reduction in panic symptoms elicited by cholecystokinin-tetrapeptide. Moreover, benzodiazepine-like effects on the activity of the hypothalamic-pituitary-adrenal axis have been observed in association with vigabatrin treatment. Small open studies in patients with panic disorder also showed an improvement in panic and anxiety with both compounds. This review summarizes our recent research on the effects of selective GABAergic treatment in experimentally induced panic and outlines the possible role of compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor for the treatment of panic and anxiety.
Zwanzger
Peter
P
Anxiety Research Unit and Anxiety Outpatient Clinic, Department of Psychiatry, Ludwig-Maximilians-Universität, Munich, Germany. zwanzger@med.uni-muenchen.de
Rupprecht
Rainer
R
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D018682:GABA Agents / Q000627:therapeutic use*; D018755:GABA Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010200:Panic / Q000502:physiology; D016584:Panic Disorder / Q000188:drug therapy* / Q000523:psychology*; D011963:Receptors, GABA-A / Q000187:drug effects
D014151:Anti-Anxiety Agents; D018682:GABA Agents; D018755:GABA Agonists; D011963:Receptors, GABA-A