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Memory enhancer

Partial inverse agonist with preference for a5 subtype

B. Modulatory site other than benzodiazepine site

Ethanol

Anxiolytic

High sensitivity (>3 mM) at a4(a5)b35d; Medium sensitivity (>30 mM) at a4(a5)p2Sd; Low sensitivity (>100 mM) at a4(a5)b3g2

Sedative

Neurosteroids (e.g., 3a,5a-THDOC)

Anxiolytic

High sensitivity at 5-containing subtypesd and at a1, a3 receptors in combination with b1

Sedative

Anesthetic

Intravenous anesthetics (Etomidate, Propofol)

Sedative

Act on receptor subtypes containing b3, i.e., mainly a2 and a3 subtypes

Anesthetic

C. GABA site

Gaboxadol

Hypnotic

Partial agonist at a,, a3 subtypes, full agonist at a5, and superagonist at a4ß35 receptorsb

aThis table is a summary from Rudolph and Möhler (2006), Möhler (2007a, 2008), and Atack (2008)

bClassical partial agonists, which do not differentiate between GABAa receptor subtypes such as Bretazenil or Pagoclone, are not considered in this review cData should be treated with caution as properties of recombinant receptors that are expressed in foreign host cells might not give an accurate reflection of their neuronal counterparts dGABA is a weak partial agonist on 8-containing receptors, which largely explains the strong modulatory response of ligands acting on 8-containing receptors. THDOC, 5a-pregnane3a,21-diol-20-one aThis table is a summary from Rudolph and Möhler (2006), Möhler (2007a, 2008), and Atack (2008)

bClassical partial agonists, which do not differentiate between GABAa receptor subtypes such as Bretazenil or Pagoclone, are not considered in this review cData should be treated with caution as properties of recombinant receptors that are expressed in foreign host cells might not give an accurate reflection of their neuronal counterparts dGABA is a weak partial agonist on 8-containing receptors, which largely explains the strong modulatory response of ligands acting on 8-containing receptors. THDOC, 5a-pregnane3a,21-diol-20-one activity, pointing to a potential deficit in GABAergic control. Indeed, in postmortem studies, GABAergic Chandelier neurons in frontal brain were found to be dysfunctional. These neurons are known to act via a2GABAA receptors. Furthermore, in mice, a deficit of a3GABAA receptors resulted in sensorimotor gating deficits and a hyperdopaminergic phenotype. These results pointed to a new GABAergic strategy in treating cognitive deficits, sensorimotor gating deficits, and possibly negative symptoms in schizophrenia. Restoration of GABAwas expected to restore oscillatory synchronicity and cognitive function. MK0777, an a2/a3 GABAa receptor modulator, was therefore tested in the treatment of schizophrenia patients. In a proof of concept study, a 4-week treatment with MK0777, as add-on to the standard antipsychotic therapy, resulted not only in an increased level of ► attention and ► working memory, but also restored the oscillatory power of the g band, when the patients performed a cognitive task. Thus, a GABA substitution therapy proved effective in reconstituting the phenotype and the biotype of cognition. This example is expected to trigger further clinical trials to support an entirely new therapeutic concept of cognitive deficits based on a2/a3 GABAa receptors (Lewis et al. 2008).

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Do Not Panic

Do Not Panic

This guide Don't Panic has tips and additional information on what you should do when you are experiencing an anxiety or panic attack. With so much going on in the world today with taking care of your family, working full time, dealing with office politics and other things, you could experience a serious meltdown. All of these things could at one point cause you to stress out and snap.

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