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Re: Are any of these new GABA meds effective?

Posted by HoldenYosarian on February 15, 2005, at 3:35:41

In reply to Re: Are any of these new GABA meds effective?, posted by sabre on February 13, 2005, at 23:13:36

> Thankyou Thankyou Thankyou, Holden.
> This is what I have been wanting to know.
> Tyrosine is one of the only supplements that have yielded any results for approx 2g/day. But the effect wears out after a few weeks and I have to go off it. I had been wondering about using Reboxetine as I can get in Australia and the gp said she was happy to prescribe it.
> SSRIs are awful, including Tryptophan.
> I started looking into GABA and have recently played around with GABA, Phenibut and Picamilon but didn't get the results I was after. I sidetracked to glutamine and have found it very stimulating esp at about 2g/day. I tried mixing 500mg with valium yesterday but the valium sedation won.
> Propanalol and glutamine are a little better but not what I'm after.
> I thought that perhaps if I found a regulator or enhancer of the glutamate to GABA conversion that I would find social ease. I've unearthed references to taurine and theanine having this addition to GABA prescription drugs.
> At the same time I also found a reference to
> It mentioned that NA and DA are modulators of glutamate to GABA conversion.
> So is this what you are talking about?
> I'll go and look up your suggestions.
> Thanks again, Holden and welcome to Babble.
> sabre

Sabre--I've included the rather abstruse study to illustrate a point...while glutamine and glutamate is technically responsible for the creation of GABA, GABA is for the most part a transitional stage through which glutamate passes
on its way to become glutamine, and is exists during only brief stages during which this process takes place, for the most part.
The study follows:
The glutamate-glutamine cycle: biochemical and molecular considerations
The metabolism of neurotransmitter glutamate and GABA is linked to a substrate cycle between neurons and astrocytes involving glutamate, GABA and glutamine (Martin 1995 , Schousboe et al. 1993 , Van den Berg 1972 ). The efficient functioning of the glutamate-glutamine cycle is made possible by the physical segregation of specific enzymes between neurons and glia and the presence of specialized amino acid transporter proteins. Glutamate and GABA released into the synapse in response to nerve terminal depolarization, bind to their respective receptors and are cleared from the interstitum by uptake into astroglia. Within astroglia, glutamate (and GABA through an indirect process) is converted to glutamine by the astroglia-specific enzyme, glutamine synthetase (GS) (Martinez-Hernandez et al. 1977 ). Glutamine is transported from astroglia into neurons and is hydrolyzed to glutamate by the mitochondrial enzyme, phosphate-activated glutaminase (PAG) (Kanamori and Ross 1995 , Kvamme and Lenda 1982 ). Thus, this pathway results in a cyclic flow of carbon between nerve terminals and glia, i.e., a glutamate-GABA-glutamine cycle. Some of the key molecular components required for the operation of this cycle are described below.

Two other neuronal transporters, EAAT4 and EAAT5, are expressed on cerebellar GABAergic Purkinje cells and in the retina, respectively, and appear to differ from their cortical counterparts in gating Cl- ions. Although the functions of the neuronal transporters are not yet clear, one of them (EAAC1) is expressed on some GABAergic nerve terminals (Kanai and Hediger 1992 , Rothstein et al. 1994 and 1996 ) where it may have a role in the supply of precursor glutamate for GABA synthesis (Sepkuty et al. 2000).
Evidence from molecular (Rothstein et al. 1996 and 1994 ) and electrophysiologic studies (Bergles and Jahr 1997 and 1998 ) indicates that the astroglial transporters clear the majority of glutamate from the synaptic cleft. As discussed subsequently, the molecular findings are consistent with in vivo NMR study results showing that glutamate uptake into astroglia and its conversion to glutamine is the predominant path for recycling of neuronal glutamate in vivo (Rothman et al. 1999 ).
GABA transport.
Astroglia and neurons possess a high capacity for the transport of GABA (Henn and Hamberger 1971 , Hertz et al. 1978 , Ryan and Roskoski 1977 ). Molecular cloning studies have identified four high affinity, Na+ and Cl--dependent, GABA transporters (GAT) in the brain (GAT1, GAT2, GAT3, GAT4/BGT-1). With the exception of GAT-3, which is expressed on astrocytes, the other GAT subtypes are expressed on both neurons and astrocytes (Minelli et al. 1995 and 1996 , Ribak et al. 1996 ). The functional roles of the different GABA transporter subtypes in the clearance of GABA from synaptic, and possibly extrasynaptic sites remain to be elucidated. Rapid metabolism of GABA in astrocytes via an active GABA-transaminase (Chan-Palay et al. 1979 , Larsson and Schousboe 1990 ) maintains GABA at a low level in these cells, resulting in a large concentration gradient between GABAergic neurons and the surrounding transporter-rich astroglia
GABA synthesis depends on glutamine for its supply of glutamate precursors in vitro and in vivo (Balazs et al. 1973 , Patel et al. 2000 , Sonnewald et al. 1993 , Van den Berg 1972 ), indicating that some fraction of GABA released from GABAergic neurons is not recycled directly back into the terminal. ('Some Fraction--meaning not much)

Astroglial metabolism of extracellular glutamate and GABA stimulates glutamine synthesis.
Glutamine synthesis in astroglia is generally considered the major net metabolic pathway for the metabolism of extracellular glutamate (Wanienski and Martin 1986 ). GABA metabolism in astroglia can also lead to glutamine synthesis. Unlike glutamate, however, GABA must be further processed in the astroglial tricarboxylic acid (TCA) cycle, a two-step reaction involving -ketoglutarate and NAD+ that converts GABA to succinic acid via GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase. The initial transamination between GABA and -ketoglutarate catalyzed by GABA-T produces glutamate, which may then proceed to formation of glutamine."

May your path be straight, or as winding as the wisdom to which you are fated...





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