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GHB Neuropharmacology

by Five


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Sometime ago, I decided to investigate exactly how GHB (gamma-hydroxybutrate) acts on the brain. I had assumed that it involved the GABAnergenic system because of their similar structures- GABA is gamma-aminobutyric acid, so they essentially differ by a NH2 and an OH (I'll spare you my ASCII molecular renditions).

This turns out not to be the case. GHB actually affects the dopamine (DA) system by preventing its release (dispersion) at the synapse. The end result is a reversable lesion (*) in the nigrostriatal and mesolimbic DA systems. Thus, a large enough dose makes a great anestetic by shutting down a rather important (at lease for consciousness) part of the brain.

Additionally, GHB also causes the neurons to make more DA. So now you've plugged the drain *and* turned up the faucet. One wonders what might happen if things were taken to the extreme: A subject (such as a rat) ingests L-DOPA to increase they available precursor for DA, ingests GHB to turn-over this precursor and accumulate it presynaptically, and, finally, applys a combination of amphetamine to release this flood of DA and cocaine to prevent its reuptake (**).

Two other interesting bits of information I located: There is another compound that seems to have the same properties as GHB. Its called (+)-HA-966. I could not seem to find a structure nor additonal information on it. Anyone? Secondly, GHB is "a naturally occuring metabolite" found in the brain. This should ease some worries. Although, I read about a "rare inborn mutation in the metabolism of GABA" called GHB aciduria. It is "unclear whether the ... main clinical symptoms of motor and mental retardation... [are] related to elevated levels of GHB". This should strengthen worries about its toxicity.

Five

Sources:

mostly "The Biochemical Basis of Neuropharmacology", 7th ed. by Cooper, et. al.

Notes: (*)- A "revesible lesion" does not mean that any sort of physical damage has happened to the brain. Rather, it is the temperary "turning off" of an area.

(**)- The author takes no legal or health responsiblities from this suggestion.

 
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