Posted by MM on February 17, 2005, at 21:18:07
In reply to Re: what do mood stabilizers do?? TRIGGER? » linkadge, posted by Phillipa on February 15, 2005, at 17:27:21
http://www.mcmanweb.com/article-236.htm
"The Mighty Two
Glutamate and GABA represent the yin-yang of the neurotransmitters, Darryle Schoepp PhD of Eli Lilly explained in a session at the 2003 American Psychiatric Association annual meeting, both present in nearly all synaptic function all over the brain, with the former acting in an excitatory capacity and the latter in an inhibitory role. The mood stabilizers are thought to act on one or the other or both.
There are two types of glutamate receptors, ionotropic (iGluR), including NMDA, kainate, and AMPA receptors; and metabotropic (mGluR), which mediate numerous chemical actions. When the NMDA receptor is working right, glutamate and glycine bind to the receptor, which opens up its corresponding ion channel and permits calcium entry into the neuron. This in turn promotes intracellular signaling essential to plasticity and survival.
Husseini Manji MD, Chief of the Laboratory of Molecular Pathophysiology at the NIMH, at the same APA session, reported what can go wrong: In response to stress and mood episodes, glutamate reuptake in the synapse is compromised, resulting in increased calcium influx through the NMDA receptors and ion channels into the neuron and the activation of certain calcium-dependent enzymes that can result in cell atrophy and death. In some patients, Dr Manji observed, their mood disorder may be fundamentally atrophic rather than symptomatic.
In an article in the May 2003 Biological Psychiatry, Dr Manji et al listed a number of experimental drugs that target the NMDA receptors. One small study found that the anesthetic, ketamine, an “NMDA receptor antagonist,” resulted in rapid improvement in depressed patients. The anticonvulsant felbamate, and a drug used in Germany to treat memory loss, memantine, are also being investigated for treating depression.
Meanwhile, over at the AMPA receptors, which are tied to MAP kinase and other processes, “AMPA receptor potentiators” (ARPs) may modulate these receptors and enhance MAP kinase activation. Several compounds are being investigated.
The mood stabilizer, Lamictal, with demonstrated efficacy for bipolar depression, is an antiglutamate agent. A drug currently on the market to treat ALS, riluzole, inhibits glutamate. A pilot study at the NIMH is underway to investigate its antidepressant effects.
GABA is formed in the brain from glutamate, glucose, and glutamine, and binds to one of two receptors on the postsynaptic neuron. GABA A receptors regulate excitability and anxiety, panic, and stress, and are the targets of benzodiazepines such as Ativan, barbiturates, and alcohol. Depressed individuals have decreased GABA in their cerebral spinal fluid and plasma.
Gerard Sanacora MD, PhD of Yale has used magnetic resonance spectroscopy to measure GABA in the brain, finding that those with melancholic depression show low GABA concentrations in the occipital cortex, while the depletion is not as pronounced for those with atypical depression, indicating a diagnostic potential for subtypes of depression (March, 2003 American Journal of Psychiatry). Before and after scans of eight patients who had ECT found a doubling of GABA, and similar scans of patients on SSRIs showed a slow rise in GABA levels in nine of 11 of them.
Julia Ross of Mood Cure fame refers to GABA as "our natural valium," and recommends it to her clients for calming down. However, as this neurotransmitter does not easily cross the blood-brain barrier, you may wind up instead with very expensive urine."
mood stabilizers affect "the mighty two"...glutamate/GABA....
What the mood stabilizer will do probably depends on which one you try. They can be good for anxiety/panic, and can also help with depression (lithium and lamictal are the ones I've heard of mostly for that).
Trileptal can help with anxiety. I'm not sure what to make of mood stabilizers sometimes, because a simple explanation is that they are the drugs that keep you from going overboard/manic/happy, so you would think of them as like a - and an antidepressant as a +, or just opposite drugs, but that's not really the case. Sometimes a depressed brain can be overexcited too, so....I can't really explain what I don't understand, but I hope this helps.
MM
poster:MM
thread:457944
URL: http://www.dr-bob.org/babble/20050217/msgs/459616.html