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Dr. Bob is Robert Hsiung, MD,
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Posted by Julie on September 22, 1999, at 12:13:58
Has anyone had experience with GABA(A) agonists in treating social phobia?
MY UNDERSTANDING AS A LAYPERSON (Don't take this as pschopharmacologist gospel)
GABA(A) receptors are the major inhibitory neurotransmitter receptors. Benzodiazepines (such as Klonopin) act to enhance GABA(A) by causing a "shift in the GABA concentration-effect curve to lower concentrations (of GABA)." That is, they effectively raise GABA levels. When GABA(A) is activated, "it increases the inward flow of chloride through the nerve cell membrane, which hyperpolarizes the membrane and inhibits neuronal firing."However, a major problem with Benzodiazepines is their impairment of short-term memory formation and recall. Recently a number of new drugs have been introduced to enhance GABA(A). They're termed anti-epileptic drugs (AED's). By the way, Clonazepam (Klonopin)is an AED. Their mechanisms include (1) direct stimulation, (2)inhibition of GABA metabolism, or (3) reduction of neuronal and/or glial GABA reuptake. Blocking GABA reuptake has been the most recently studied mechanism for increase whole brain GABA. Two recently introduced drugs include Tiagabine (trade name Gabitril) (decreases GABA reuptake), and Progabide (enhances GABA content). Another GABA(A)agonist, Pagoclone (Interneuron Pharmaceuticals) was shown in a 1997 study to significantly reduce the frequency of panic attacks. Typically, those drugs most effective in treating panic disorder (Phenelzine, Clonazepam) are also the most effective in treating social phobia. Lastly, Gabapentin is another drug which has not been shown to be of significant efficacy in treating social phobia. It "is structurally related to GABA, but does not interact with GABA receptors, it is not metabolized to GABA or to GABA agonists, and it is not an inhibitor of GABA uptake or degradation." Its mechanism of action has not been established.
The hydrazine MAOI's, such as Phenelzine and Isocarboxazid, have been shown to significantly increase whole brain GABA levels. They are effective in treating panic and social phobia. The non-hydrazine MAOI's (such as Tranylcypromine) do not affect GABA. They have not been shown to be efficacious in treating social phobia or panic. Further, the SSRI's, which have some relative efficacy in treating panic disorder and social phobia appear to have an indirect effect on GABA.
On a final note, GABA, taken orally does not cross the blood-brain barrier. Perhaps there is a placebo effect to those who take it. Further, GABA taken sublingually (under the tongue)has no better chance of crossing the blood-brain barrier.
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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