indication

Used as a general anesthetic, to treat conditions such as insomnia, clinical depression, narcolepsy, and alcoholism, and to improve athletic performance.

pharmacology

GHB has at least two distinct binding sites in the central nervous system. GHB is an agonist at the newly-characterized GHB receptor, which is excitatory, and it is a weak agonist at the GABAB receptor, which is inhibitory. GHB is a naturally-occurring substance that acts in a similar fashion to some neurotransmitters in the mammalian brain. GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire.

mechanism of action

GHB reaches much higher concentrations in the brain and activates GABAB receptors, which are primarily responsible for its sedative effects. GHB receptors are densely expressed in many areas of the brain, including the cortex and hippocampus, and these are the receptors that GHB displays the highest affinity for. There has been somewhat limited research into the GHB receptor; however, there is evidence that activation of the GHB receptor in some brain areas results in the release of glutamate, the principal excitatory neurotransmitter. Activation of both the GHB receptor and GABA(B) is responsible for the addictive profile of GHB. GHB's effect on dopamine release is biphasic,[19] low concentrations stimulate dopamine release via the GHB receptor.[20] Higher concentrations inhibit dopamine release via GABA(B) receptors as do other GABA(B) agonists such as baclofen and phenibut.[21] After an initial phase of inhibition, dopamine release is then increased via the GHB receptor. This explains the paradoxical mix of sedative and stimulatory properties of GHB, as well as the so-called "rebound" effect, experienced by individuals using GHB as a sleeping agent, wherein they awake suddenly after several hours of GHB-induced deep sleep. That is to say that, over time, the concentration of GHB in the system decreases below the threshold for significant GABAB receptor activation and activates predominantly the GHB receptor, leading to wakefulness.

toxicity

At higher doses, GHB may induce nausea, dizziness, drowsiness, agitation, visual disturbances, depressed breathing, amnesia, unconsciousness, and death.

half life

30 to 60 minutes

route of elimination

Animal studies indicate that metabolism is the major elimination pathway for sodium oxybate, producing carbon dioxide and water via the tricarboxylic acid (Krebs) cycle and secondarily by beta-oxidation. Succinic acid enters the Krebs cycle where it is metabolized to carbon dioxide and water. Fecal and renal excretion is negligible. 5% renal elimination.