ABSTRACT
The original treatment indicated for those suffering from neurotic anxiety was to employ psychotherapy to facilitate changes in behavior and coping with stressful events. A spectrum of somatic treatments "from cathartics and emetics to opium and "strengthening tonics", from atropine and digitalis to potassium bromide and chloral hydrate, from barbiturates to benzodiazepines", to serotonergics, came to be used as well [1]. The Food and Drug Administration originally approved many gamma-aminobutyric acid (GABA) facilitating drugs since the 1960s for anxiety treatment. The 1980s evidenced the approval of a few serotonergic treatments that cornered the prescribing market and the front line of most treatment protocols. More recently, GABAergic drugs are making a return in the treatment of anxiety disorders. The following paper details the pharmacodynamic history of treating anxiety and also updates the reader as to the newer GABA-based approaches mentioned above.
Subject(s)
Anxiety Disorders/drug therapy , Pharmacology/trends , Anti-Anxiety Agents/therapeutic use , Double-Blind Method , GABA Modulators/classification , GABA Modulators/history , GABA Modulators/pharmacology , History, 20th Century , Humans , Pharmacology/history , Randomized Controlled Trials as Topic , Selective Serotonin Reuptake Inhibitors/classification , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic useABSTRACT
Drugs modulating gamma-aminobutyric acid (GABA) transmission via the benzodiazepine (BZ) site on the gamma-aminobutyric acid type A (GABAA) receptor have been in widespread use for more than 40 years to treat anxiety, epilepsy, and sleep disorders. These drugs have been shown to be safe, well tolerated, and effective although the mechanism by they produce a myriad of pharmacologic effects remains elusive. In recent years it has been discovered that, although the GABAA receptor is widely distributed in the brain, the substructure and composition of the receptor differs from between brain regions. Termed "GABAA receptor subtypes" their discovery leads to speculation that different subtypes may mediate specific effects of BZs such as anxiety or sedation. The phenotypic analysis of transgenic knock-in and knock-out mice in which particular GABAA receptors were rendered insensitive to the effects of BZ while others were unaffected confirmed this speculation. Subsequently, subtype-specific GABAA ligands were developed that, for example, retained the anxiolytic effects of BZs but were devoid of their sedative effects. Therefore, it may be possible to develop effective anxiolytic compounds that have a much reduced side-effect profile compared with existing drugs.
Subject(s)
Anxiety/drug therapy , Epilepsy/drug therapy , GABA Modulators , Receptors, GABA-A/drug effects , Sleep Wake Disorders/drug therapy , Binding Sites/drug effects , GABA Modulators/classification , GABA Modulators/pharmacology , GABA Modulators/therapeutic use , HumansABSTRACT
ISSUE: Anticonvulsants are not a single therapeutic class, but are composed of multiple distinct subclasses with different mechanisms of action, efficacies, and side effects.
